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Title: A Multicenter, Open-Label Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ICP-723 in Patients With Advanced Solid Tumors | Condition: Advanced Solid Tumors | Keywords: | Summary: | Description: N/A | ArmGroups: [{'label': 'ICP-723', 'type': 'EXPERIMENTAL', 'interventionNames': ['Drug: ICP-723']}] | Interventions:[{'type': 'DRUG', 'name': 'ICP-723', 'description': '3+3 dose escalation', 'armGroupLabels': ['ICP-723']}] | PrimaryOutcomes: [{'measure': 'Incidence and severity of dose-limiting toxicity (DLT), adverse events (AEs), and serious adverse events (SAEs). Frequency of dose interruptions, reductions and intensity', 'timeFrame': 'through study completion, an average of 1.5 years.'}] | SecondaryOutcomes: [{'measure': 'Objective response rate (ORR) determined using RECIST 1.1 criteria.', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Disease control rate (DCR) determined using RECIST 1.1 criteria.', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Peak concentration (Cmax)', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Time to reach peak concentration (Tmax)', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Half-life (t1/2)', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Area under the plasma concentration-time curve (AUC0-∞ and AUC0-t)', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Apparent clearance (CL/F)', 'timeFrame': 'Through study completion, an average of 4 years'}, {'measure': 'Apparent volume of distribution (Vz/F),', 'timeFrame': 'Through study completion, an average of 4 years'}] |
Title: A Randomized Phase II Trial Evaluating the Endocrine Activity and Efficacy of Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Receiving Letrozole for Primary Endocrine Responsive Breast Cancer | Condition: Breast Cancer Invasive Nos | Keywords: Premenopausal patients, ER-positive, PgR+ (>50%), HER2-negative or not amplified | Summary: | Description: RATIONALE Preoperative chemotherapy enables breast-conserving surgery for some patients with breast cancer, and it might be advantageous in several other ways. For example, the response to primary treatment may be used as a prognostic marker, since it has been demonstrated to be associated with a longer disease-free survival (DFS) compared with no response. In particular the degree of response (pathological complete remission (pCR)) predicts overall outcome in terms of DFS.
However, pCR can be achieved only in a minority of patients with estrogen receptor (ER)-positive disease. Studies in the medical literature indicate that pCR rates range from 2% to 10% in those patients whose tumors express ER suggesting that objective response and decrease of Ki67 must be considered within this subset of tumors.
The results of phase II studies and randomized phase III trials have clearly shown that preoperative endocrine therapy is a feasible and safe option among patients with hormone-receptor positive tumors. Letrozole has been shown to induce greater rates of clinical responses and of breast-conserving surgery in postmenopausal women as compared with tamoxifen.
In premenopausal women with ER and progesterone receptor (PgR) positive breast cancer, the preoperative endocrine therapy includes a combination of a gonadotropin-releasing hormone analogue (GnRH) plus tamoxifen. Recent studies suggest that neoadjuvant endocrine therapy with a combination of GnRH analogue and aromatase inhibitors (AIs: letrozole or anastrozole) is effective in selected premenopausal patients. The GnRH analogue, also known as a luteinizing hormone-releasing hormone agonist (LHRH agonist) or LHRH analogue, is a synthetic peptide drug modeled after the human hypothalamic gonadotropin-releasing hormone (GnRH). A GnRH analogue is designed to interact with the GnRH receptor and modify the release of pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for therapeutic purposes. Upon administration of a GnRH analogue, an initial stimulating action of the hypophysis occurs - termed a "flare" effect - which eventually causes a paradoxical and sustained drop in gonadotropin secretion. This second effect has been termed "downregulation" and can be observed after about 10 days. While this phase is reversible following cessation of medication, it can be maintained when GnRH agonists' use is continued for a long time. For a select group of patients, there is a delay of approximately 2-4 months before downregulation of the gonadotropins is observed.
Degarelix (INN) or degarelix acetate (USAN) (tradename: Firmagon) is a hormonal therapy approved for the treatment of prostate cancer. Since testosterone, a male hormone, promotes the growth of many prostate tumors, reduction of circulating testosterone to very low (castration) levels is often the treatment goal in the management of advanced prostate cancer. Degarelix, an antagonist of GnRH, has immediate onset of action through binding to GnRH receptors in the pituitary gland and blocking their interaction with GnRH. The result is a fast and profound reduction in LH, FSH and in turn, testosterone suppression. Its activity in suppressing the ovaries of premenopausal women might therefore be faster than other GnRH analogues, possibly by several weeks. The probable difference in onset of action could have significant clinical value for patients who are candidates for short-term neoadjuvant endocrine treatment.
TRANSLATIONAL RESEARCH A tumor block from the diagnostic core biopsy and one from final surgery will be collected and banked for central review and future translational research at the IBCSG Tissue Bank hosted by the European Institute of Oncology in Milan, Italy.
PATIENT-REPORTED SYMPTOMS The patient-reported symptoms (PRS) will be assessed using the Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-ES) comprising 18 items (each has score range from 0 to 4) with a possible maximum total score of 72. Functional Assessment of Chronic Illness Therapy (FACIT) guidelines will be used for scoring and interpretation of the FACT-ES total score. Patients will be asked to complete a PRS Form at baseline (prior to randomization), at day 1 of cycle 2, at day 1 of cycle 4, and prior to surgery.
The objectives are
* To assess the differences in PRS score over time between the two treatment arms
* To correlate the estradiol (E2) levels and total PRS score measured on day 1 of cycle 2 and day 1 of cycle 4 of triptorelin or degarelix administration
* To summarize each of the 18 individual (endocrine symptom) items of the FACT-ES descriptively over time as the proportion of patients with "clinically significant" symptoms (those scoring 3 or 4)
STRATIFICATION Stratification will be performed according to:
- Age(in years): less than or equal to 39 versus 40 or more
STATISTICAL CONSIDERATIONS To achieve the primary objective, E2 levels will be determined centrally from samples taken at day 1 of the first treatment cycle before the administration of the first dose of degarelix or triptorelin (baseline), and thereafter at 24 and 72 hours, 7 days and 14 days after the first injection, and on day 1 of cycles 2 to 6 before the administration of degarelix or triptorelin.
For sample size calculation, we assume that the cumulative percentages of patients in the triptorelin arm achieving optimal ovarian function suppression (defined as E2 ≤2.72 pg/mL or ≤10 pmol/L) will be 30% within 2 weeks, 60% within 4 weeks and 75% within 8 weeks, and that degarelix will provide more rapid suppression (i.e., 60% within 2 weeks, 95% within 4 weeks and 100% within 8 weeks). Enrollment of 25 patients in each treatment arm will provide at least 90% power to detect a difference in time to optimal ovarian function suppression between the two groups, using a two sample log-rank test with a two-sided significance level of 0.05.
Randomized patients who receive at least one injection of triptorelin or degarelix will be included in the primary analysis. The primary endpoint will be compared between the two treatment arms using a stratified two-sample log-rank test, with age as stratification factor. The distribution of the primary endpoint will be summarized using the method of Kaplan-Meier and the two-sided 95% confidence interval (CI) for the difference in proportion of patients who achieve optimal ovarian function suppression between the two treatment arms at the end of the 1st, 2nd and 4th cycle will also be provided.
The toxicity, changes in Ki67 expression levels, the Preoperative Endocrine Prognostic Index (PEPI) score at the time of surgery, disease response, node-negative disease status at surgery and breast-conserving surgery (BCS) rate will also be summarized and differences assessed between treatment arms with confidence intervals.
The primary endpoint for patient-reported symptoms (PRS) analysis is the total PRS score measured at baseline, day 1 of cycle 2 and day 1 of cycle 4 of triptorelin or degarelix administration, and prior to surgery. The differences in PRS measurements between the two treatment arms over time will be explored using the repeated measures analysis based on generalized estimating equation (GEE) model. | ArmGroups: [{'label': 'triptorelin + letrozole', 'type': 'EXPERIMENTAL', 'description': 'Arm A: Triptorelin 3.75 mg i.m. on day 1 every 28 days for 6 cycles + letrozole 2.5 mg/day orally for 6 cycles', 'interventionNames': ['Drug: triptorelin', 'Drug: letrozole']}, {'label': 'degarelix + letrozole', 'type': 'EXPERIMENTAL', 'description': 'Arm B: Degarelix 240 mg s.c. on day 1 of cycle 1, followed by 80 mg s.c. on day 1 of cycles 2 to 6 + letrozole 2.5 mg every day orally for 6 cycles', 'interventionNames': ['Drug: degarelix', 'Drug: letrozole']}] | Interventions:[{'type': 'DRUG', 'name': 'triptorelin', 'description': 'Triptorelin 3.75 mg injected into the muscle on day 1 every 28 days for 6 cycles (1 cycle= 28 days)', 'armGroupLabels': ['triptorelin + letrozole'], 'otherNames': ['decapeptyl']}, {'type': 'DRUG', 'name': 'degarelix', 'description': 'Degarelix 240 mg injected under the skin given as two injections of 120 mg on the first day of treatment, followed by injection of 80 mg on day 1 of cycles 2 to 6 (1 cycle=28 days)', 'armGroupLabels': ['degarelix + letrozole'], 'otherNames': ['firmagon']}, {'type': 'DRUG', 'name': 'letrozole', 'description': 'Letrozole 2.5 mg orally every day for 6 cycles', 'armGroupLabels': ['degarelix + letrozole', 'triptorelin + letrozole'], 'otherNames': ['femara']}] | PrimaryOutcomes: [{'measure': 'Time to Optimal Ovarian Function Suppression', 'description': 'Time from the first injection of degarelix or triptorelin to the first assessment of centrally assessed 17-β-estradiol (E2) level in the range of optimal ovarian function suppression (≤2.72 pg/mL or ≤10 pmol/L) during the 6 cycles of neoadjuvant treatments.', 'timeFrame': 'up to 24 weeks'}] | SecondaryOutcomes: [{'measure': 'Ki67 Proliferation Marker Changes', 'description': 'The percent change in Ki67 expression from pre-treatment diagnostic (baseline) biopsy to surgery, calculated as (surgery-baseline)/baseline\\*100.', 'timeFrame': 'Before day1 of cycle 1 and surgery'}, {'measure': 'Preoperative Endocrine Prognostic Index (PEPI) Score', 'description': 'Preoperative Endocrine Prognostic Index (PEPI) is the sum of the risk points (tumor size, nodal status, Ki67 level, ER status) with a 0-12 score representing the best prognostic feature (0 being the best score; 12 being the worst score), as previously determined to be associated with recurrence-free survival.', 'timeFrame': 'After 24 weeks or the time of surgery'}, {'measure': 'Best Overall (Disease) Response', 'description': 'Based on WHO tumor measurement and response criteria \\[1\\], measured from the start of treatment across all time points until disease progression or the end of 6 cycles of neoadjuvant therapies, whichever comes first. Response was determined by the IBCSG Head of Medical Affairs. An internal review (IR) form was created to record the final determination on best overall response. Confirmation of partial or complete response by an additional scan was not required in this trial. Best overall response was assessed based on changes in tumor size from baseline to the assessments after 3 and after 6 cycles (denoted as day 1 of cycle 4 and prior to surgery respectively) as measured physically by caliper or ruler and as measured by breast tumor imaging (i.e., bilateral mammography and breast ultrasound).', 'timeFrame': 'From day 1 of cycle 1 across all time points until disease progression'}, {'measure': 'Percentage of Patients With Node-negative Disease at Surgery', 'description': 'The number of lymph nodes assessed at surgery minus the number of positives nodes identified, equal to zero.', 'timeFrame': 'During surgery, an average of 2 hours'}, {'measure': 'Percentage of Patients Who Underwent Breast-Conserving Surgery (BCS)', 'description': 'Whether or not patient undergoes BCS (per Surgery form).', 'timeFrame': 'During surgery, an average of 2 hours'}, {'measure': 'Patient-reported Symptoms (PRS) Outcomes', 'description': 'The patient-reported symptoms (PRS) will be assessed using the Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-ES) comprising 18 items (each has score range from 0 to 4) with a possible minimum total score of 0 and maximum total score of 72 (72 is best). Functional Assessment of Chronic Illness Therapy (FACIT) guidelines will be used for scoring and interpretation of the FACT-ES total score.', 'timeFrame': 'At baseline, day 1 of cycle 2 and cycle 4 and prior to surgery; cycle 4 reported'}] |
Title: A Single Arm, Open Lable and Single Site Early Phase I Clinical Trial to Evaluate the Safety, Cell Kinetics and Initial Efficacy About Anti-claudin18.2 the Specificity of Chimeric Antigen Receptor T Cells in the Advanced Gastric / Esophagogastric Junction Adenocarcinoma and Pancreatic Cancer Subjects | Condition: CAR T-Cell Therapy | Keywords: | Summary: | Description: Single Site, single arm and open label design are adopted. The dose increment is based on the traditional "3 + 3" method, and the initial dose is set to 0.5 × 10\^6 car-t cells / kg, and 3 \~ 6 subjects are expected to be included in each dose group. DLT was observed within 28 days after infusion. One suject of each dose group was enrolled first, and there was no DLT within 14 days before entering the next subject. If the subject had DLT within 14 days, the investigator can evaluate whether the dose group continued to be enrolled and the time interval of the next subject. After completing the safety observation of 3 subjects who meet the DLT evaluation and analysis set in each dose group, they can be increased to the next dose when there is no DLT; If one subject in the first three cases has DLT, another three subjects need to be selected into the dose group (but the researcher can also decide whether to continue to be selected into the dose group according to the actual situation of the subjects). In the process of dose increase, if DLT occurs in ≥ 2 / 3 or ≥ 2 / 6 subjects in a dose group, the dose increase stops. | ArmGroups: [{'label': 'HEC-016', 'type': 'EXPERIMENTAL', 'description': 'Anti-claudin18.2 the Specificity of Chimeric Antigen Receptor T Cells', 'interventionNames': ['Drug: HEC-016(0.5×10^6 CAR-T Cells)', 'Drug: HEC-016(0.5×10^6.5 CAR-T Cells)', 'Drug: HEC-016(0.5×10^7 CAR-T Cells)']}] | Interventions:[{'type': 'DRUG', 'name': 'HEC-016(0.5×10^6 CAR-T Cells)', 'description': 'The initial dose is set to 0.5 × 10\\^6 car-t cells / kg, and 3 \\~ 6 subjects are expected to be included in the dose group. DLT was observed within 28 days after cell infusion.', 'armGroupLabels': ['HEC-016']}, {'type': 'DRUG', 'name': 'HEC-016(0.5×10^6.5 CAR-T Cells)', 'description': 'The Second dose is set 0.5 × 10\\^6.5 car-t cells / kg, and 3 \\~ 6 subjects are expected to be included in the dose group.', 'armGroupLabels': ['HEC-016']}, {'type': 'DRUG', 'name': 'HEC-016(0.5×10^7 CAR-T Cells)', 'description': 'The Third dose is set 0.5 × 10\\^7 car-t cells / kg, and 3 \\~ 6 subjects are expected to be included in the dose group.', 'armGroupLabels': ['HEC-016']}] | PrimaryOutcomes: [{'measure': 'DLT', 'description': 'Dose limiting toxicity', 'timeFrame': 'Within 28 days after the first infusion'}] | SecondaryOutcomes: N/A |
Title: Pilot Cohort Study of Rb-82 Myocardial PET Imaging to Evaluate Coronary Microvascular Dysfunction in Men With Prostate Cancer Receiving Androgen-Deprivation Therapy | Condition: Prostate Cancer | Keywords: | Summary: | Description: N/A | ArmGroups: [{'label': 'Observational', 'description': 'To determine the feasibility of using myocardial PET imaging', 'interventionNames': ['Device: myocardial PET imaging']}] | Interventions:[{'type': 'DEVICE', 'name': 'myocardial PET imaging', 'description': 'using myocardial PET imaging as a means to assess cardiovascular risk in men with prostate cancer planned for androgen-deprivation therapy with external beam radiation therapy', 'armGroupLabels': ['Observational']}] | PrimaryOutcomes: [{'measure': 'number of subjects who successfully complete Rb-82 myocardial PET Imaging assessments', 'timeFrame': '12-18 months'}] | SecondaryOutcomes: N/A |
Title: Phase II Trial of Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for Multiple Brain Metastases in Non-small Cell Lung Cancer | Condition: Brain Metastases, Non-small Cell Lung Cancer | Keywords: brain metastases, hippocampus-avoidance, whole-brain radiation therapy, simultaneous integrated boost | Summary: | Description: Introduction Lung cancer has high incidence and mortality rates. NSCLC is the most prevalent form accounting for 85% of all lung cancer cases with approximately 40% of individuals developing brain metastases during the illness\[1-4\]. With advancements in therapies like targeted therapy and immunotherapy, the incidence of brain metastases have raised paralleled by a rise in survival rates of NSCLC\[5\]. And NSCLC patients with brain metastases only 2 to 3 months of natural survival\[6\]. Therefore, it is urgent to improve the prognosis and intracranial control of NSCLC patients with brain metastases.
Brain metastases patients of NSCLC should be treated with local treatment on the basis of systemic treatment. For patients of NSCLC with brain metastases who are not suitable for targeted therapy or with progressing intracranial post targeted therapy, radiotherapy emerges as a significant therapeutic\[7\].Stereotactic radiosurgery (SRS) alone should be offered to patients with one to three unresected brain metastases for patients with asymptomatic brain metastases and no systemic therapy options.While the standard treatment for multiple brain metastases (≥4) remains controversial.
WBRT is used to be a common therapy in multiple brain metastases prolonging survival of patients to 6 months\[8\]. But WBRT comes with neurotoxic effects, notably cognitive impairment affecting memory and learning\[9, 10\]. This cognitive decline is mainly attributed to hippocampal damage, a crucial region for learning and memory\[11\]. The RTOG0933 and NRG Oncology CC001 trials have demonstrated that HA-WBRT effectively safeguards cognitive function and enhances the quality of life in patients with brain metastases\[12, 13\]. Furthermore, considering the tolerated dose of normal brain tissue, the dose of WBRT was low (30Gy/10F) with only 60% intracranial local control rate\[14\]. The landmark RTOG9508 trial has demonstrated that WBRT in combination with boosted metastases can improve local intracranial control\[15-19\].
Prokic et al. reported that the simultaneous integrated boost during WBRT (WBRT+SIB) demonstrated superior hippocampal sparing and biological benefits of fractionation over sequential integrated boost\[20\]. Advancements in radiotherapy techniqueshave led to the innovative HA-WBRT+SIB strategy, delivering higher dosages to existing metastases while minimizing radiation exposure to the hippocampus. However, evidence for the application of HA-WBRT+SIB in multiple (≥4) brain metastases of NSCLC remains insufficient. Therefore, this study aims to investigate the efficacy and safety of HA-WBRT+SIB in patients with multiple brain metastases of NSCLC.
Method Patient population This is a prospective, single-center, and single-arm phase II clinical study, which has received the Ethical Committee approval of Nanjing Medical University Affiliated Cancer Hospital (Jiangsu Cancer Hospital) and performed following the principles of the Helsinki Declaration. Informed consent was obtained from each participant before study initiation.
The prospective cohort consisted ofpatients who underwent HA-WBRT + SIB at the Department of Radiation Oncology, Jiangsu Cancer Hospital. Eligible patients were adults (aged 18-75 years) diagnosed with NSCLC, with a KPS (Karnofsky performance status) ≥70, at least four brain metastases visible on MRI (magnetic resonance imaging) outside a 5-mm margin around the bilateral hippocampi, not suitable for targeted therapy or progressing intracranial post targeted therapy. Ineligible participants had a history of conditions affecting cognitive function (including mental illness, brain trauma, and Alzheimer\'s disease), other primary malignant tumors, uncontrolled systemic disease, uncontrolled extracranial sites of gross disease,and suitable for targeted therapy.
The control group (the retrospective WBRT cohort): Firstly, a total of 741 individuals of brain metastases who had received radiotherapy were identified. 688 unsuitable patients were then excluded. As a consequence, 53 patients who received conventional WBRT were retrospectively selected between January 2017 and December 2020, meeting the inclusion and exclusion criteria of the prospective HA-WBRT+SIB cohort (Figure1 Flow chart).
Clinicopathologic data collected included age, sex, number and longest diameters of brain metastases, pathological type, extracranial metastases status, KPS score, prior brain metastases treatment and prior targeted therapy.
Radiation Treatment Planning of HA-WBRT+SIB Patients scanned planning CT (computed tomography) of the whole brain region with a thickness of 1 mm by thermoplastic mask immobilization. To delineate hippocampal contouring based on RTOG0933, 3.0T brain MRI with T1 contrast was carried out two days before planning CT and coregistered with CT scans rigidly (Supplementary Figure 1). The GTVbrain metastases (Gross tumor volume of metastases) encompassed intracranial tumor lesions visible on MRI. To identify the PTVbrain metastases (Planned target volume of metastases), GTVbrain metastases was subsequently followed by a uniform 1 mm expansion. A 5-mm three-dimensional border around the hippocampus served as the HAR (Hippocampal avoidance region). Patients with multiple brain metastases of NSCLC received HA-WBRT (30Gy in 12 fractions, Dmax of thehippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤ 12Gy) and a SIB with 48Gy in 12 fractions. The prescribed dose covered 95% isodose. Eclipse v15.5 software (Varian, USA) facilitated treatment plan calculations. Twenty-three patients (100%) in the HA-WBRT+SIB cohort were treated with non-coplanar IMRT (intensity-modulated radiation therapy) designed with nine homogeneous fields. The radiotherapy techniques used in the WBRT cohort include traditional 2-dimensional planning (6.5%) and 3-dimensional planning based on CT (93.5%). Treatment was administered using a TureBeam linear accelerator (Varian, USA) in 6-MV FFF X-ray mode. Hausdorffdistance between PTVbrain metastases and bilateral hippocampi was measured using Velocity (Varian, USA).
Follow-Up and Study endpoint The prospective HA-WBRT+SIB cohort underwent 3.0T MRI scans to be evaluated following RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria. Regular follow-up visits occurred every 3 months post-radiotherapy, involving physical examinations, chest and abdomen CT scans, brain MRI, laboratory tests, and other examinations and toxicity assessments via CTCAE5.0 (Common Terminology Criteria for Adverse Events 5.0). Cognitive endpoints were assessed using the HVLT-R DR score at the baseline and then at 2 and 4 month post-HA-WBRT+SIB.
Follow-up visits for the WBRT retrospective cohort were approximately every three months (according to clinical practice), including physical examination, chest and abdomen CT scans, brain MRI, and laboratory tests.
Primary endpoint: Intracranial local progression-free survival time (iLPFS)was determined as the time from HA-WBRT+SIB initiation to death, existing intracranial metastases progression, or last follow-up. Intracranial progression-free survival time (iPFS) was measured from HA-WBRT+SIB initiation to existing or new metastases intracranial progression, death, or last follow-up. Cognitive function was measured by the relative change in HVLT-R DR score from the start of HA-WBRT+SIB to 4 months after the start of HA-WBRT+SIB. Secondary endpoint: OS (Overall survival) was described as the time from initiation of radiation to the last follow-up or death. The cumulative incidence of local intracranial failure was measured as the progression of existing intracranial metastases. Cumulative incidence of intracranial failure was described as the progression of existing or new intracerebral metastases.
Statistical analysis R software (version 4.1.0; The R Foundation for Statistical Computing, Vienna, Austria) was utilized for all statistical analyses. Propensity score matching (PSM) (1:2; HA-WBRT+SIB: WBRT = 23:46), with a caliper size of 0.01, adjusted for variables like age, sex, KPS scores, number and longest diameters of brain metastases, extracranial metastases status, prior brain metastases treatment and prior targeted therapy. The Kaplan-Meier method was used to draw the survival curve of iLPFS and iPFS. And HA-WBRT+SIB cohort and WBRT cohort were compared by log-rank test. Cumulative incidence of local intracranial failure and intracranial failure were estimated for cumulative incidences by the Aalen-Johansen estimator, considering death as a competing risk. Statistical significance was set at P \< 0.05. | ArmGroups: [{'label': 'Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost', 'type': 'EXPERIMENTAL', 'description': 'HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions)', 'interventionNames': ['Radiation: ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost']}] | Interventions:[{'type': 'RADIATION', 'name': 'ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost', 'description': 'hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost', 'armGroupLabels': ['Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost']}] | PrimaryOutcomes: [{'measure': 'Intracranial local progression-free survival time (iLPFS)', 'description': 'determined as the time from HA-WBRT+SIB initiation to death, existing intracranial metastases progression, or last follow-up.', 'timeFrame': 'From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 months'}] | SecondaryOutcomes: [{'measure': 'Intracranial progression-free survival time (iPFS)', 'description': 'measured from HA-WBRT+SIB initiation to existing or new metastases intracranial progression, death, or last follow-up.', 'timeFrame': 'From date of enrollment until the date of progression of existing or new metastases intracranial or date of death from any cause, whichever came first, assessed up to 20 months'}, {'measure': 'Cognitive function', 'description': 'was measured by the relative change in HVLT-R DR score from the start of HA-WBRT+SIB to 4 months after the start of HA-WBRT+SIB.', 'timeFrame': 'From enrollment to the end of treatment at 4 weeks'}, {'measure': 'OS (Overall survival)', 'description': 'described as the time from initiation of radiation to the last follow-up or death', 'timeFrame': 'From date of enrollment until the date of death from any cause, whichever came first, assessed up to 20 months'}, {'measure': 'The cumulative incidence of local intracranial failure', 'description': 'measured as the progression of existing intracranial metastases', 'timeFrame': 'From date of enrollment until the date of progression of existing intracranial metastases， assessed up to 20 months'}, {'measure': 'Cumulative incidence of intracranial failure', 'description': 'described as the progression of existing or new intracerebral metastases.', 'timeFrame': 'From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 months'}] |
Title: Assessment of Health Related Quality of Life in Patients Treated for Rectal Cancer | Condition: Rectal Cancer, Colon Cancer, Anal Cancer | Keywords: | Summary: | Description: There exists little published data studying the health related quality of life (HRQOL) of patients treated for the rectal cancer. Patients are commonly treated with surgery preceded or followed by chemo radiotherapy. Patients chart review and questionnaires administered during follow-up exam or by mailing will be use to compile data comparing the HRQOL of the two study groups(Preoperative versus Post operative chemotherapy).
Our Radiation Oncologist will also informed all the new pts. under going radiotherapy regarding this study and will encourage them in become part of our study population. The prospective study will help us in increasing the number of participants and also it give us an opportunity following the patients as they go through their treatment.
Through the use of department databases, a cohort or rectal cancer patients treated at Stanford will be identified. Patients demographics, treatment received ,disease outcomes, and treatment associated complications will be compiled from available data. HRQOL questionnaires will be answered through a mailing or during clinic visits. Treatment outcomes, toxicities and overall quality of life of preoperative and postoperative chemo radiotherapy treatment group will be compared in relation to the lesion location. | ArmGroups: N/A | Interventions:[{'type': 'BEHAVIORAL', 'name': 'Questionnaire', 'description': 'Questionnaire form to be completed by patient', 'otherNames': ['Research survey']}] | PrimaryOutcomes: N/A | SecondaryOutcomes: N/A |
Title: Pilot Study of Ketamine-assisted Talk Therapy for Demoralization in Advanced GI Cancer | Condition: Pancreatic Ductal Adenocarcinoma, Pain, Acute, Gastrointestinal Cancers, Demoralization | Keywords: Medication assisted therapy, ketamine | Summary: | Description: PRIMARY OUTCOMES:
I. To assess the feasibility of Meaning and Purpose therapy combined with oral ketamine (K-MaP) in demoralized participants.
SECONDARY OUTCOMES:
I. To characterize the preliminary safety and tolerability of K-MaP in demoralized participants with stage 3 or 4 gastrointestinal (GI) cancers.
II. To assess the magnitude and durability of improvement from randomization in psychosocial distress.
III. To assess the magnitude and durability of improvement from randomization in pain.
IV. To assess the magnitude of change from randomization in opioid analgesic use.
V. To assess the magnitude and durability of change from randomization in interoceptive awareness
EXPLORATORY OBJECTIVES:
I. To assess how the participant's subjective experiences with ketamine may be related to clinical outcomes.
II. To assess how participants' stage of cancer may be related to clinical outcomes.
III. To assess how the participants' changes in measures of cardiac interoception following receipt of ketamine may be related to subjective experiences with ketamine and clinical outcomes.
OUTLINE:
Adult participants with advanced stage GI cancers receiving care at the Helen Diller Family Comprehensive Cancer Center (HDFCCC) will be randomized in a 1:1 ratio to one of two double-blinded conditions consisting of a single drug treatment and several therapy sessions. Participants will be followed up to 35 days (+/-2 days) after ketamine administration. | ArmGroups: [{'label': 'Group A (K-MaP)', 'type': 'EXPERIMENTAL', 'description': 'Participants will receive 0.5mg/kg of Ketamine orally with an equivalent quantity of placebo via an intramuscular injection on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.', 'interventionNames': ['Drug: Ketamine', 'Behavioral: Meaning and Purpose therapy', 'Other: Placebo', 'Other: Questionnaires']}, {'label': 'Group B (K-Map)', 'type': 'EXPERIMENTAL', 'description': 'Participants will receive 0.5mg/kg of Ketamine IM with a placebo oral solution on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.', 'interventionNames': ['Drug: Ketamine Injectable Product', 'Behavioral: Meaning and Purpose therapy', 'Other: Placebo', 'Other: Questionnaires']}] | Interventions:[{'type': 'DRUG', 'name': 'Ketamine', 'description': 'Given orally (PO)', 'armGroupLabels': ['Group A (K-MaP)'], 'otherNames': ['Ketalar', 'Ketalar Hydrocholoride']}, {'type': 'DRUG', 'name': 'Ketamine Injectable Product', 'description': 'Given intramuscularly (IM)', 'armGroupLabels': ['Group B (K-Map)'], 'otherNames': ['Ketalar', 'Ketalar Hydrocholoride']}, {'type': 'BEHAVIORAL', 'name': 'Meaning and Purpose therapy', 'description': 'In-person sessions', 'armGroupLabels': ['Group A (K-MaP)', 'Group B (K-Map)'], 'otherNames': ['MaP', 'MaP therapy', 'Psychotherapy']}, {'type': 'OTHER', 'name': 'Placebo', 'description': 'Given PO or IM', 'armGroupLabels': ['Group A (K-MaP)', 'Group B (K-Map)']}, {'type': 'OTHER', 'name': 'Questionnaires', 'description': 'Questionnaires will be given over the course of the study', 'armGroupLabels': ['Group A (K-MaP)', 'Group B (K-Map)']}] | PrimaryOutcomes: [{'measure': 'Proportion eligible versus screened participants.', 'description': 'The rate of recruitment is defined as the proportion of eligible participants who participate compared to the number of total participants who were screened or signed consent but did not meet eligibility criteria will be reported.', 'timeFrame': 'Up to 28 days'}, {'measure': 'Proportion of participants who complete therapy', 'description': 'Proportion of enrolled participants completing K-MaP intervention and all Demoralization Scale II (DS-II) assessments will be reported.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Frequency of participant responses to intervention acceptability', 'description': 'The participants will provide qualitative feedback on the acceptability of the intervention via a 20-minute interview with the study team upon study termination. Frequency of responses will be categorized and reported by arm.', 'timeFrame': '1 day'}] | SecondaryOutcomes: [{'measure': 'Percentage of participants reporting treatment-emergent adverse events', 'description': 'The percentage of participants in each arm reporting treatment-related adverse events will be reported. Pre-determined criteria for assessment of tolerability to K-MaP include zero treatment-related serious adverse events, and all other adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Percentage of participants with clinically significant changes in blood pressure', 'description': 'At time of ketamine administration, participants blood pressure will be monitored for any clinically significant changes. The percentage of participants with a clinically significant change in blood pressure from pre-medication administration to end of study visit will be reported.', 'timeFrame': '1 day'}, {'measure': 'Percentage of participants with clinically significant changes in heart rate', 'description': 'At time of ketamine administration, participants heart rate will be monitored for any clinically significant changes. The percentage of participants with a clinically significant change in heart rate from pre-medication administration to end of study visit will be reported.', 'timeFrame': '1 day'}, {'measure': 'Mean scores on the Challenging Experience Questionnaire (CEQ) over time', 'description': 'The CEQ is a 26-item, self-reported measure of challenging experiences with psychedelics. The CEQ assesses seven factors: grief (5 items), fear (6 items), subjective experience of death (2 items), insanity (3 items), isolation (3 items), physical distress (5 items), and paranoia (2 items). Each of the 26 items is scored on a 5-point Likert scale (0 = "None; not at all" to 5 = "Extreme \\[more than ever before in my life\\]"). Participants are asked to rate each item based on the degree to which each item was experienced. A higher total CEQ score indicates greater psychologically adverse reactions to psilocybin.', 'timeFrame': '1 day'}, {'measure': 'Mean clinician-rated scores on the Global Clinical impression of severity (CGI-S) over time', 'description': 'The CGI is a 3-item clinician-administered measure developed by the National Institute of Mental Health to assess clinical change in participants in psychopharmacology trials. This study will be using the Global Impression of Severity item ("Considering your total clinical experience with participants with demoralization, how would you rate this participant\'s level of demoralization at this time?"), on the scale from "1 = Normal, not at all demoralized" to "7 = Among the most extremely demoralized participants" to assess change in demoralization.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean clinician-rated scores on the Demoralization Interview (DI) over time', 'description': 'The DI is a clinician-rated measure of demoralization which consists of 14-items designed from items of the Demoralization Scale II. The items measure events that occurred over the past 2 weeks, which are scored on a 3-point scale ranging from 0 to 2. Scores are calculated by adding each item score, for a total score range of 0 to 28. Higher scores indicate a greater degree of demoralization.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean clinician-rated scores on the GRID-Hamilton Depression Rating Scale (GRID-HAMD) over time', 'description': 'The 6-item Hamilton Depression Rating Scale (HAMD-6) is a validated, brief, clinician-rated measure of the core symptoms of major depression. With permission from authors (the International Society for Central Nervous System Drug Development (ISCDD)) a modified, 6-items version of the HAMD-6 in the GRID-HAMD format to will be used by clinicians to create a brief, responsive and reliable measure of core depression symptoms of participants. Responses on the items will range from 0=absent; 1=mild; 2=moderate; 3=severe; 4=incapacitating and scores will be summed to create a total score. The higher the total score the more severe the depression symptoms of the participant.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Proportion of participants with reported demoralization based on the Diagnostic Criteria in Psychosomatic Research (DCPR) Demoralization scale.', 'description': 'The DCPR is a structured, clinician-administered, interview regarding various psychosomatic conditions and will be administered to participants over the course of the study. Clinicians will record the rates of demoralization as present or not per participant', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Demoralization Scale II (DS-II) over time', 'description': 'The DS-II is a measure of demoralization which consists of 16-items designed from items of the Demoralization Scale II. The items measure events that occurred over the past 2 weeks, which are scored on a 3-point scale ranging from 0 to 2. Scores are calculated by adding each item score, for a total score range of 0 to 32. Higher scores indicate a greater degree of demoralization.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Patient Health Questionnaire 9 (PHQ-9) over time', 'description': 'The Patient Health Questionnaire-9 (PHQ-9) is used to measure depression symptoms. The total Patient Health Questionnaire-9 (PHQ-9) score is calculated by combining the responses of the participant on questions addressing how bothered the participant has been by various problems over the past 2 weeks. Each of the 9 items is scored on a scale of 0 ("Not bothered at all") to 4 ("Nearly every day"). A total score of 5-9=\'Mild Depression Symptoms", 10-14="Minor Depression, Major Depression (mild), or Dysthymia", 15-19="Major Depression, moderately severe", and \\>20="Major Depression".', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Generalized Anxiety Disorder 7 (GAD-7) over time', 'description': 'The GAD-7 is a seven-item instrument that is used to measure or assess the severity of generalized anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all," "several days," "more than half the days," and "nearly every day," respectively, and then adding together the scores for the seven questions. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. When used as a screening tool, further evaluation is recommended when the score is 10 or greater.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Functional Assessment of Chronic Illness Therapy Palliative Care, 14 Item Version (FACIT-Pal-14) (FACIT-Pal-14) over time', 'description': 'The FACIT-Pal-14 is a 14-item, self-report measure of quality of life in palliative care participants. The measure has a 7-day recall period with responses to items which fall on a 5-point Likert scale, with scores ranging from 0 = "Not at all" to 4 = "Very much". Scores are summed to create a total score of 0 to 56, with higher scores indicating a greater quality of life.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Brief-Pain Inventory Short Form (BPI-SF) over time', 'description': "The BPI-SF is a 9-item questionnaire used to assess the severity of pain and the impact of pain on activities of daily living over a recall period of 24 hours. Pain severity is assessed across four sub-scales; 'worst pain', 'least pain', 'average pain' and 'current pain'. A pain score for each subscale is presented separately. Scales are rated on a scale of 0 to 10 (0 = no pain; 10 = pain as bad as one can imagine). A composite score for pain severity is calculated as the mean of the four severity items. Question 9 comprises a 7-item interference scale. Questions assess the level to which pain interferes with general activity, walking, work, mood, enjoyment of life, relations with others and sleep on a scale of 0 to 10 (0 = does not interfere; 10 = completely interferes). Mean interference score will be calculated as an average of the seven subparts of question 9 where at least four of the seven items are completed.", 'timeFrame': 'Up to 49 days'}, {'measure': 'Proportion of participants reporting any use of opioids', 'description': 'Using the Morphine Milligram Equivalents (MME) calculation, participants cumulative daily dose of opioids will be calculated for the past 24 hours at each study visit. The proportion of participants with any reported opioid use at any of the study visits will be reported.', 'timeFrame': 'Up to 49 days'}, {'measure': 'Mean scores on the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2)', 'description': 'The MAIA-2 is a validated a widely used questionnaire to measure interoceptive awareness. This measure consists of 37-items using a 6-point Likert scale (0 = "Never" to 5 = "Always"). The MAIA-2 has demonstrated good internal consistency and reliability for the evaluation of clinical mind-body interventions, with higher scores indicating increased awareness.', 'timeFrame': 'Up to 49 days'}] |
Title: Efficacy and Safety of Anlotinib Combined With Platinum Plus Pemetrexed in T790M Mutation Negative Metastastic Non-squamous Non-small-cell Lung Cancer After Progression on First-line EGFR TKI: a Phase II, Muti-center, Single Arm Study | Condition: Lung Cancer Metastatic | Keywords: non small cell lung cancer, anlotinib, pemetrexed, T790M negative | Summary: | Description: Anlotinib, an oral highly potent tyrosine-kinase inhibitor targeting VEGFR、PDGFR、FGFR and c-kit，has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer(NSCLC).
In the phase Ⅲ study ALTER0303, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months. Therefore,we envisage using anlotinib plus platinum plus pemetrexed treat the EGFR wild-type metastatic non-small cell lung cancer patients who were failure in the treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS.
The study is divided into two stages，phase I use a dose escalation trial design to explore the safety, tolerability, dose-limiting toxicities(DLT), Maximum Tolerable Dose(MTD), A cohort of 3\~6 subjects will be enrolled at each dose level, If 0 of 3 or ≤ 1 of 6 subjects experience a DLT, the phase I trial will move ahead to the next dose until ≥ 2 of 6 subjects experience a DLT，and the current dose will be considered the MTD. Following completion of the dose escalation trial and determination of MTD（Phase I）, a single arm study including 44 subjects may be enrolled to further evaluate safety, tolerability, and efficacy of anlotinib in combination with platinum plus pemetrexed in the same target population（phase II）. Phase II is to designed to explore the anti-tumor activity of anlotinib combined with platinum plus pemetrexed in T790M mutation negative metastatic non-squamous non-small cell lung cancer(NSCLC) after the failure of EGFR-TKI. | ArmGroups: [{'label': 'Anlotinib + AP/PC', 'type': 'EXPERIMENTAL', 'interventionNames': ['Drug: anlotinib 8mg + AP/PC', 'Drug: anlotinib 10mg + AP/PC', 'Drug: anlotinib 12mg + AP/PC', 'Drug: anlotinib + AP/PC']}] | Interventions:[{'type': 'DRUG', 'name': 'anlotinib 8mg + AP/PC', 'description': 'anlotinib 8mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.', 'armGroupLabels': ['Anlotinib + AP/PC'], 'otherNames': ['Pemetrexed/Cisplatin or Pemetrexed/Carboplatin']}, {'type': 'DRUG', 'name': 'anlotinib 10mg + AP/PC', 'description': 'anlotinib 10mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.', 'armGroupLabels': ['Anlotinib + AP/PC'], 'otherNames': ['Pemetrexed/Cisplatin or Pemetrexed/Carboplatin']}, {'type': 'DRUG', 'name': 'anlotinib 12mg + AP/PC', 'description': 'anlotinib 12mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.', 'armGroupLabels': ['Anlotinib + AP/PC'], 'otherNames': ['Pemetrexed/Cisplatin or Pemetrexed/Carboplatin']}, {'type': 'DRUG', 'name': 'anlotinib + AP/PC', 'description': 'anlotinib doses to be determined following the completion of Phase I of the study, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.', 'armGroupLabels': ['Anlotinib + AP/PC']}] | PrimaryOutcomes: [{'measure': 'Progression-free survival (PFS)', 'description': 'PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.', 'timeFrame': 'Up to 24 months'}, {'measure': 'Dose limiting toxicity (DLT)', 'description': 'Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria', 'timeFrame': 'Estimated about 6 months'}, {'measure': 'Maximum tolerance dose (MTD)', 'description': 'Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.', 'timeFrame': 'Estimated about 6 months'}] | SecondaryOutcomes: [{'measure': 'Objective response rate(ORR)', 'description': 'To determine ORR of Anlotinib Anlotinib combined with Platinum-based Pemetrexed in T790M mutation negative Advanced NSCLC. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.', 'timeFrame': 'Up to 24months'}, {'measure': 'Disease Control Rate (DCR)', 'description': 'Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.', 'timeFrame': 'Up to 24months'}, {'measure': 'Duration of Response (DOR)', 'description': 'Defined as the the time from first confirmed CR or PR until the first date of either objective disease progression or death due to any cause.', 'timeFrame': 'Up to 24months'}, {'measure': 'Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability)', 'description': 'Number of Participants with Adverse Events as a Measure of Safety and Tolerability', 'timeFrame': 'Until 21 day safety follow-up visit'}] |
Title: Phase 2 Study of Alpelisib and Fulvestrant for PIK3CA-mutated Estrogen Receptor (ER)-positive Endometrioid Endometrial Cancers | Condition: Endometroid Endometrial Cancer | Keywords: advanced, persistent, recurrent, PIK3CA-mutated, ER-postive | Summary: | Description: N/A | ArmGroups: [{'label': 'Apelisib and Fulvestrant', 'type': 'EXPERIMENTAL', 'description': 'alpelisib 300mg orally daily of each 28-day cycle fulvestrant 500mg IM on Day 1 and Day 15 of Cycle 1, then 500mg IM on Day 1 of each 28-day cycle.', 'interventionNames': ['Drug: Alpelisib Pill', 'Drug: Fulvestrant injection']}] | Interventions:[{'type': 'DRUG', 'name': 'Alpelisib Pill', 'description': 'Kinase inhibitor', 'armGroupLabels': ['Apelisib and Fulvestrant'], 'otherNames': ['Piqray']}, {'type': 'DRUG', 'name': 'Fulvestrant injection', 'description': 'estrogen receptor agonist', 'armGroupLabels': ['Apelisib and Fulvestrant'], 'otherNames': ['Faslodex']}] | PrimaryOutcomes: [{'measure': 'Response rate', 'description': 'To determine the objective response rate of the combination of alpelisib and fulvestrant in patients with advanced, persistent or recurrent PIK3CA-mutated ER-positive endometrioid endometrial cancer. Respnse criteria based on RECIST Version 1.1 (complete or partial response).', 'timeFrame': 'Response to treatment is assessed by RECIST Version 1.1 criteria every 8 weeks with CT scan or MRI through completion of treatment (complete or partial response). Patients receive treatment until disease progression and are followed for 5 years.'}] | SecondaryOutcomes: [{'measure': 'Drug Toxicity (Side Effects)', 'description': 'Drug toxicity will be assessed by collecting adverse event data every 4 weeks', 'timeFrame': 'Side effects are monitor from the start of treatment to discontinuation of treatment assessed every 4 weeks. Patients are treated until disease progression and are followed for 5 years.'}] |
Title: A Phase 1 Study of ENMD-2076 in Patients With Relapsed or Refractory Hematological Malignancies | Condition: Relapsed or Refractory Hematological Malignancies | Keywords: Leukemia, Hematologic neoplasms | Summary: | Description: N/A | ArmGroups: [{'label': '1', 'type': 'EXPERIMENTAL', 'interventionNames': ['Drug: ENMD-2076']}] | Interventions:[{'type': 'DRUG', 'name': 'ENMD-2076', 'description': 'capsule, dose escalation, taken orally, daily in 28 day cycles', 'armGroupLabels': ['1']}] | PrimaryOutcomes: [{'measure': 'Define the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of oral daily ENMD 2076 by evaluation of adverse events', 'timeFrame': 'Day 1 through first cycle of therapy'}] | SecondaryOutcomes: [{'measure': 'Safety and toxicity of repeated oral dosing of ENMD 2076', 'timeFrame': 'Throughout study participation'}, {'measure': 'Describe any preliminary evidence of anti-cancer effects of ENMD-2076 in patients with hematological malignancies', 'timeFrame': 'monthly'}] |
Title: An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies | Condition: Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer, Hepatocellular Carcinoma | Keywords: metastatic, advanced, immuno-oncology, vascular endothelial growth factor (VEGF), angiogenesis, PD-1, PD-L1 | Summary: | Description: N/A | ArmGroups: [{'label': 'Ramucirumab + MEDI4736 (NSCLC)', 'type': 'EXPERIMENTAL', 'description': 'In phase 1a (DLT phase), ramucirumab plus MEDI4736 given intravenously (IV) every 3 weeks (q3w) of a 21 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.\n\nIn phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q3w. Participants may continue to receive study treatment until discontinuation criteria are met.', 'interventionNames': ['Drug: Ramucirumab', 'Drug: MEDI4736']}, {'label': 'Ramucirumab + MEDI4736 (Gastric/GEJ)', 'type': 'EXPERIMENTAL', 'description': 'In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV every 2 weeks (q2w) of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.\n\nIn phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.', 'interventionNames': ['Drug: Ramucirumab', 'Drug: MEDI4736']}, {'label': 'Ramucirumab + MEDI4736 (HCC)', 'type': 'EXPERIMENTAL', 'description': 'In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV q2w of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.\n\nIn phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.', 'interventionNames': ['Drug: Ramucirumab', 'Drug: MEDI4736']}] | Interventions:[{'type': 'DRUG', 'name': 'Ramucirumab', 'description': 'Administered IV', 'armGroupLabels': ['Ramucirumab + MEDI4736 (Gastric/GEJ)', 'Ramucirumab + MEDI4736 (HCC)', 'Ramucirumab + MEDI4736 (NSCLC)'], 'otherNames': ['LY3009806', 'IMC-11121B', 'Cyramza']}, {'type': 'DRUG', 'name': 'MEDI4736', 'description': 'Administered IV', 'armGroupLabels': ['Ramucirumab + MEDI4736 (Gastric/GEJ)', 'Ramucirumab + MEDI4736 (HCC)', 'Ramucirumab + MEDI4736 (NSCLC)']}] | PrimaryOutcomes: [{'measure': 'Number of Participants with Dose Limiting Toxicities (DLTs)', 'timeFrame': 'Cycle 1 (up to 28 days)'}] | SecondaryOutcomes: [{'measure': 'Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)', 'timeFrame': 'Baseline to Disease Progression (Approximately 22 Months)'}, {'measure': 'Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)', 'timeFrame': 'Baseline to Disease Progression (Approximately 22 Months)'}, {'measure': 'Duration of Response (DoR)', 'timeFrame': 'Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 22 Months)'}, {'measure': 'Time to First Response (TTR)', 'timeFrame': 'Baseline to Date of CR or PR (Approximately 22 Months)'}, {'measure': 'Progression Free Survival (PFS)', 'timeFrame': 'Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months)'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months)'}, {'measure': 'Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736', 'timeFrame': 'Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)'}, {'measure': 'PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736', 'timeFrame': 'Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months)'}, {'measure': 'Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies', 'timeFrame': 'Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)'}, {'measure': 'Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies', 'timeFrame': 'Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)'}] |
Title: A Phase II/III Trial of Neoadjuvant FOLFOX With Selective Use of Combined Modality Chemoradiation Versus Preoperative Combined Modality Chemoradiation for Locally Advanced Rectal Cancer Patients Undergoing Low Anterior Resection With Total Mesorectal Excision (PROSPECT) | Condition: Colorectal Cancer | Keywords: stage IIA rectal cancer, stage IIIA rectal cancer, stage IIIB rectal cancer | Summary: | Description: OUTLINE: This is a multicenter, phase II/III study. Patients are stratified according to ECOG performance status (0 or 1 vs 2) and randomized to 1 of 2 treatment regimens. Patients will receive full supportive care while on this study.
OBJECTIVES:
Primary
1. Phase II component: To assure that neoadjuvant FOLFOX followed by selective use of 5FUCMT group (Group 1) maintains the current high rate of pelvic R0 resection and is consistent with non-inferiority for time to local recurrence (TLR).
2. Phase III component: To compare neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) to standard 5FUCMT (Group 2) with respect to the primary endpoint of the Disease-Free Survival (DFS).
Secondary
1. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard group 5FUCMT (Group 2) with respect to the proportion of patients who achieve a pathologic complete response (pCR) at the time of surgical resection.
2. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to overall survival.
3. To evaluate and compare the adverse event profile and surgery complications between two groups.
4. To estimate the proportion of patients in the selective group (Group 1) who receive: 1) pre-operative 5FUCMT; 2) post-operative 5FUCMT; 3) either pre- or post-operative 5FUCMT.
5. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to Local Recurrence (TLR)
6. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to Neoadjuvant Response Score (NAR)
Event monitoring of patients will continue up to 8 years post randomization. | ArmGroups: [{'label': 'Group 1', 'type': 'EXPERIMENTAL', 'description': 'Patients will receive FOLFOX chemotherapy once every two weeks for 6 cycles total over a period of 12 weeks. After completing FOLFOX chemotherapy, the patient will have an MRI scan or endorectal ultrasound (ERUS) to examine the tumor. If the tumor has not decreased in size by at least 20%, the patient will receive 5FUCMT (radiation with chemotherapy). If the tumor has decreased in size by 20%, then the patient will proceed directly to surgery.\n\nIf all borders of the tumor are normal post surgery, then the patient receives six additional cycles of FOLFOX chemotherapy. If all borders of the tumor are not normal then the patient receives chemoradiation therapy for 5.5 weeks after surgery. After chemoradiation, additional cycles of FOLFOX or similar chemotherapy will be recommended for 4 cycles or 8 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.', 'interventionNames': ['Drug: FOLFOX (chemotherapy)', 'Other: 5 FUCMT (chemoradiation)', 'Procedure: surgery', 'Procedure: magnetic resonance imaging or endorectal ultrasound']}, {'label': 'Group 2', 'type': 'ACTIVE_COMPARATOR', 'description': 'Patients receive 5FUCMT including chemotherapy and radiation therapy for 5.5 weeks. Patients will be given either 5-fluorouracil or capecitabine and radiation therapy. After the chemoradiation therapy is completed, patients will proceed directly to surgery. Post-surgery, patients will receive FOLFOX chemotherapy once every two weeks for 8 cycles total over a period of 16 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.', 'interventionNames': ['Drug: FOLFOX (chemotherapy)', 'Other: 5 FUCMT (chemoradiation)', 'Procedure: surgery']}] | Interventions:[{'type': 'DRUG', 'name': 'FOLFOX (chemotherapy)', 'description': 'Oxaliplatin 85 mg/m\\^2 IV over 2 hours on day 1, leucovorin 400 mg/m\\^2 bolus IV over 2 hours on day 1 and 5-fluorouracil 400 mg/m\\^2 bolus over 5-15 minutes then 2400 mg/m\\^2 continual over 46-48 hours total dose IV on days 1-2. The treatment schedule repeats based on the group. Dose modifications are allowed based on adverse events.', 'armGroupLabels': ['Group 1', 'Group 2']}, {'type': 'OTHER', 'name': '5 FUCMT (chemoradiation)', 'description': '5-fluorouracil 225 mg/m\\^2 per day continuous IV infusion administered concurrently with radiation therapy for 5 or 7 days per week OR capecitabine 825 mg/m\\^2 twice daily administered orally and concurrently with radiation therapy for 5 days per week. Dose modifications are allowed based on adverse events.', 'armGroupLabels': ['Group 1', 'Group 2']}, {'type': 'PROCEDURE', 'name': 'surgery', 'description': 'low anterior resection with total mesorectal excision', 'armGroupLabels': ['Group 1', 'Group 2']}, {'type': 'PROCEDURE', 'name': 'magnetic resonance imaging or endorectal ultrasound', 'armGroupLabels': ['Group 1']}] | PrimaryOutcomes: [{'measure': 'Pelvic R0 Resection Rate', 'description': 'Number of Participants with Pelvic R0 Resection', 'timeFrame': 'Up to 5 years'}, {'measure': 'DFS', 'description': 'Disease-free Survival (DFS): The distribution of DFS by group will be estimated using the method of Kaplan-Meier. 5 year disease free rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. Log-rank test will be used to compare DFS between two treatment groups. Hazard ratio with confidence interval will be estimated based on Cox proportional hazard model. The Cox proportional hazard model will be used for multivariate analysis.', 'timeFrame': 'Up to 5 years'}] | SecondaryOutcomes: [{'measure': 'Pathologic Complete Response', 'description': "Pathologic Complete Response (pCR): The pCR rate is defined as number of patients who achieve pCR divided by total number of patients included in the analysis population (see definition in Section 16.3.3.1) in each group. Patients who didn't undergo surgery will be classified as non-pCR. Point estimate and confidence interval (according to approach of Duffy and Santner) will be calculated by treatment groups. Chi-square test will be used to compare the pCR rates between groups.", 'timeFrame': 'Up to 8 years'}, {'measure': 'Overall Survival', 'description': 'Overall Survival (OS): OS is defined as time from randomization to the date of death due to all causes. The distribution of OS by group will be estimated using the method of Kaplan-Meier. Five year survival rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. Logrank test will be used to compare OS between two treatment groups. Hazard ratio with confidence interval will be estimated based on Cox proportional hazard model. The Cox proportional hazard model will be used for multivariate analysis.', 'timeFrame': 'Up to 5 years'}, {'measure': 'Rates of Receiving Pre- or Post-operative 5FUCMT', 'description': 'Rates of Receiving 5FUCMT: For selective group patients, the proportion of patients who received 1) pre-operative 5FUCMT, 2) post-operative 5FUCMT, 3) either pre or post-operative 5FUCMT, and confidence intervals (according to approach of Duffy and Santner) will be reported.', 'timeFrame': 'Up to 5 years'}, {'measure': 'Local Recurrence (TLR):', 'description': 'Time to Local Recurrence (TLR): The distribution of TLR by group will be estimated using the method of Kaplan-Meier. 5 year local recurrence free rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. The comparison of the cumulative incidence of local recurrence between groups, treating distant recurrence and death as competing risks using the test of Gray (Annals of Statistics, 1988) will be conducted.', 'timeFrame': 'Up to 5 years'}, {'measure': 'Neoadjuvant Rectal Score', 'description': 'neoadjuvant rectal (NAR) score =\\[5 \\* pN - 3(cT - pT) + 12\\]\\^2/9.61. cT is an element of the set {1, 2, 3, 4}, pT is in {0, 1, 2, 3, 4}, and pN is in {0, 1, 2}. cT clinical tumor stage, pT pathologic tumor stage, pN pathologic nodal stage. Low (NAR \\<8), intermediate (NAR = 8-16), and high (NAR \\>16). Low is better and high is worse.', 'timeFrame': 'Up to 5 years'}] |
Title: A Randomized Phase 2 Study of Combination Atezolizumab and CDX-1127 (Varlilumab) With or Without Addition of Cobimetinib in Previously Treated Unresectable Biliary Tract Cancers | Condition: Metastatic Distal Bile Duct Adenocarcinoma, Metastatic Gallbladder Carcinoma, Metastatic Intrahepatic Cholangiocarcinoma, Recurrent Distal Bile Duct Adenocarcinoma, Recurrent Gallbladder Carcinoma, Recurrent Intrahepatic Cholangiocarcinoma, Stage IV Distal Bile Duct Cancer AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Unresectable Liver Carcinoma | Keywords: | Summary: | Description: PRIMARY OBJECTIVES:
I. To assess the response rate (ORR) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib.
II. To assess the progression free survival (PFS) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib in patients with unresectable, pre-treated biliary cancers.
II. To assess overall survival (OS) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib.
III. To determine the effect of combination atezolizumab and CDX-1127 (varlilumab) +/- cobimetinib on T cell subpopulations systemically and intratumorally.
CORRELATIVE OBJECTIVES:
I. To explore the effect of atezolizumab and CDX-1127 (varlilumab) +/- cobimetinib on local and systemic immune activation pathways, immune suppressive pathways, and cytokine/chemokine signaling in peripheral blood and within the tumor microenvironment.
II. To assess whether atezolizumab and CDX-1127 (varlilumab) clearance at baseline and over time correlate with clinical outcomes (ORR, PFS and OS) and the presence of cachexia.
III. To assess immunogenicity by monitoring for the presence of anti-drug antibodies (ADA) to both atezolizumab and CDX-1127 (varlilumab).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive cobimetinib orally (PO) once daily (QD) on days 1-21 of each cycle, atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15 of each cycle, and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.
ARM B: Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.
After completion of study treatment, patients are followed up at 30 days and then every 3 months until death, withdrawal of consent, or study closure. | ArmGroups: [{'label': 'Arm A (cobimetinib, atezolizumab, varlilumab)', 'type': 'EXPERIMENTAL', 'description': 'Patients receive cobimetinib PO QD on days 1-21 of each cycle, atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle, and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.', 'interventionNames': ['Biological: Atezolizumab', 'Procedure: Biopsy', 'Procedure: Biospecimen Collection', 'Drug: Cobimetinib', 'Procedure: Computed Tomography', 'Procedure: Magnetic Resonance Imaging', 'Drug: Varlilumab']}, {'label': 'Arm B (atezolizumab, varlilumab)', 'type': 'EXPERIMENTAL', 'description': 'Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.', 'interventionNames': ['Biological: Atezolizumab', 'Procedure: Biopsy', 'Procedure: Biospecimen Collection', 'Procedure: Computed Tomography', 'Procedure: Magnetic Resonance Imaging', 'Drug: Varlilumab']}] | Interventions:[{'type': 'BIOLOGICAL', 'name': 'Atezolizumab', 'description': 'Given IV', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['MPDL 3280A', 'MPDL 328OA', 'MPDL-3280A', 'MPDL3280A', 'MPDL328OA', 'RG 7446', 'RG-7446', 'RG7446', 'RO 5541267', 'RO-5541267', 'RO5541267', 'Tecentriq']}, {'type': 'PROCEDURE', 'name': 'Biopsy', 'description': 'Undergo tumor biopsy', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['BIOPSY_TYPE', 'Bx']}, {'type': 'PROCEDURE', 'name': 'Biospecimen Collection', 'description': 'Undergo blood sample collection', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['Biological Sample Collection', 'Biospecimen Collected', 'Specimen Collection']}, {'type': 'DRUG', 'name': 'Cobimetinib', 'description': 'Given PO', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)'], 'otherNames': ['Cotellic', 'GDC 0973', 'GDC-0973', 'GDC0973', 'MEK Inhibitor GDC-0973', 'XL 518', 'XL-518', 'XL518']}, {'type': 'PROCEDURE', 'name': 'Computed Tomography', 'description': 'Undergo a CT scan', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['CAT', 'CAT Scan', 'Computed Axial Tomography', 'Computerized Axial Tomography', 'Computerized axial tomography (procedure)', 'Computerized Tomography', 'Computerized Tomography (CT) scan', 'CT', 'CT Scan', 'tomography']}, {'type': 'PROCEDURE', 'name': 'Magnetic Resonance Imaging', 'description': 'Undergo MRI', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['Magnetic Resonance', 'Magnetic Resonance Imaging (MRI)', 'Magnetic resonance imaging (procedure)', 'Magnetic Resonance Imaging Scan', 'Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance', 'MR', 'MR Imaging', 'MRI', 'MRI Scan', 'MRIs', 'NMR Imaging', 'NMRI', 'Nuclear Magnetic Resonance Imaging', 'sMRI', 'Structural MRI']}, {'type': 'DRUG', 'name': 'Varlilumab', 'description': 'Given IV', 'armGroupLabels': ['Arm A (cobimetinib, atezolizumab, varlilumab)', 'Arm B (atezolizumab, varlilumab)'], 'otherNames': ['CDX 1127', 'CDX-1127', 'CDX1127', 'Immunoglobulin G1, Anti-(Human CD Antigen CD27) (Human Monoclonal CDX-1127 Clone 1f5 Heavy Chain), Disulfide with Human Monoclonal CDX-1127 Clone 1f5 Kappa-chain, Dimer']}] | PrimaryOutcomes: [{'measure': 'Overall response rate (ORR)', 'description': 'Will be defined as the proportion of response evaluable subjects who have a complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria at any time during the study.', 'timeFrame': 'Up to 2 years'}, {'measure': 'Progression free survival (PFS)', 'description': 'Will be summarized descriptively using Kaplan-Meier plots, and compared between arms using log-rank tests.', 'timeFrame': 'Time from date of randomization to time of disease progression or death, assessed up to 2 years'}] | SecondaryOutcomes: [{'measure': 'Overall survival (OS)', 'description': 'Will be summarized descriptively using the Kaplan-Meier method. Median overall survival will be reported and the associated 95% confidence interval will be estimated.', 'timeFrame': 'Time from start of study treatment to time of death, assessed up to 2 years'}, {'measure': 'Change in T-cell populations', 'description': 'The density of CD8+ T cells in each treatment group, at baseline and after treatment, will be visualized using boxplots, and described using summary statistics including means and standard deviation presented with 95% confidence intervals. A student t-test or nonparametric Wilcoxon rank-sum test will be used to determine whether the increase in CD8+ T cells is greater in treatment arm B (combination atezolizumab and CDX-1127 (varlilumab) plus cobimetinib) than in treatment arm A (atezolizumab and CDX-1127 \\[varlilumab\\]).', 'timeFrame': 'Baseline up to 2 years'}, {'measure': 'Pharmacokinetic analysis', 'description': 'Analysis of the activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted.', 'timeFrame': 'Up to 2 years'}, {'measure': 'Immunogenicity', 'description': "Analysis of an agent's ability to provoke an immune response (humoral and/or cell-mediated) in the subject.", 'timeFrame': 'Up to 2 years'}] |
Title: Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT) With a GNRH Agonist vs. Dose Escalated Radiation Therapy and Enhanced ADT With a GNRH Agonist and TAK-700 For Men With High Risk Prostate Cancer | Condition: Prostate Cancer | Keywords: adenocarcinoma of the prostate, stage I prostate cancer, stage IIA prostate cancer, stage IIB prostate cancer, stage III prostate cancer, stage IV prostate cancer | Summary: | Description: OBJECTIVES:
Primary
* To evaluate the difference in overall survival of patients with clinically localized prostate cancer with unfavorable prognostic features between a) standard treatment (androgen-deprivation therapy \[ADT\] + radiotherapy) and b) standard treatment with the addition of 24 months of steroid 17alpha-monooxygenase TAK-700 (TAK-700).
Secondary
* To characterize differences between the treatment groups with respect to incidence of unexpected grade ≥ 3 adverse events and/or clinically significant decrement in patient-reported quality of life (QOL) among subjects treated with TAK-700.
* To compare rates and cumulative incidence of biochemical control (freedom from PSA failure), local/regional progression, and distant metastases.
* To compare rate and cumulative incidence of clinical failure, defined as prostate-specific antigen (PSA) \> 25 ng/mL, documented local disease progression, regional or distant metastasis, or initiation of ADT.
* To compare prostate cancer-specific survival and other-cause mortality.
* To compare the change in severity of fatigue as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue short form.
* To compare changes in patient-reported QOL as measured by Expanded Prostate Cancer Index Composite (EPIC).
* To assess quality-adjusted survival using the EQ-5D.
* To compare nadir and average serum testosterone at 12 and 24 months during treatment.
* To compare changes in hemoglobin A1C, fasting glucose, and fasting insulin during 24 months of systemic treatment and during the first three years of follow-up.
* To compare changes in fasting lipid levels during 24 months of treatment and during the first three years of follow-up.
* To compare changes in body mass index (BMI) during 24 months of treatment and during the first three years of follow-up.
* To compare the incidence of adverse events ascertained via CTCAE version 4.
* To compare the rate of recovery of testosterone to \> 230 ng/dL (accepted threshold for supplementation) after 12 and 24 months of follow-up.
* To compare the median time to recovery of testosterone to \> 230 ng/dL during the first five years of follow-up.
* To assess cumulative incidence of relevant clinical survivorship endpoints including new diagnosis of type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, or osteoporotic fracture.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to risk group (see Disease Characteristics) and type of radiation therapy (RT) boost (intensity-modulated RT (IMRT) vs brachytherapy). Patients are randomized to 1 of 2 treatment arms.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter. | ArmGroups: [{'label': 'ADT + RT', 'type': 'ACTIVE_COMPARATOR', 'description': 'Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.', 'interventionNames': ['Drug: GnRH agonist', 'Drug: Anti-androgen', 'Radiation: Radiation therapy']}, {'label': 'TAK-700 + ADT + RT', 'type': 'EXPERIMENTAL', 'description': 'TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.', 'interventionNames': ['Drug: GnRH agonist', 'Drug: Anti-androgen', 'Drug: TAK-700', 'Radiation: Radiation therapy']}] | Interventions:[{'type': 'DRUG', 'name': 'GnRH agonist', 'description': "LHRH agonists are administered with a variety of techniques. The manufacturer's instructions should be followed. Begins within 6 weeks after registration (if not started prior) at same time as anti-androgen and TAK-700 (if applicable).", 'armGroupLabels': ['ADT + RT', 'TAK-700 + ADT + RT'], 'otherNames': ['LHRH analog', 'leuprolide', 'goserelin', 'buserelin', 'triptorelin', 'Gonadotropin-releasing hormone (GnRH) Agonist', 'LHRH agonist']}, {'type': 'DRUG', 'name': 'Anti-androgen', 'description': 'Starts at same time as GnRH agonist, ends at end of radiation therapy. Either flutamide (orally 250 mg three times a day) or bicalutamide (orally 50 mg once a day).', 'armGroupLabels': ['ADT + RT', 'TAK-700 + ADT + RT'], 'otherNames': ['flutamide', 'bicalutamide', 'androgen suppression']}, {'type': 'DRUG', 'name': 'TAK-700', 'description': '300 mg twice daily (BID) (600 mg per day) orally, continuously for 2 years starting with ADT.', 'armGroupLabels': ['TAK-700 + ADT + RT']}, {'type': 'RADIATION', 'name': 'Radiation therapy', 'description': 'Starts 8-10 weeks after initiation of ADT. Initially 45 Gy (1.8 Gy / fraction) to prostate and pelvic lymph nodes delivered with 3DCRT/IMRT, then a boost using intensity-modulated radiation therapy (IMRT), low dose rate (LDR) brachytherapy, or high dose rate (HDR) brachytherapy.', 'armGroupLabels': ['ADT + RT', 'TAK-700 + ADT + RT']}] | PrimaryOutcomes: [{'measure': 'Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)', 'description': 'Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from secondary (original protocol) to primary. Biochemical failure will be defined by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or the initiation of salvage androgen deprivation therapy. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}] | SecondaryOutcomes: [{'measure': 'Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol)', 'description': 'Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from primary (original protocol) to secondary. Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Percentage of Participants With Grade 3 or Higher Adverse Events', 'description': 'Time to grade 3 or higher adverse event (event) is defined as time from randomization to the date of first event, last known follow-up (censored), or death without failure (competing risk). Event rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Percentage of Participants With Local Progression', 'description': 'Local recurrence (failure) is defined as biopsy proven recurrence within the prostate gland. Time to failure is defined as time from randomization to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates reported.'}, {'measure': 'Percentage of Participants With Distant Metastases', 'description': 'Distant metastases (failure) is defined as imaging or biopsy demonstrated evidence for systemic recurrence. Biopsy was not required, however it was encouraged in absence of a rising PSA. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here. Note, the protocol lists this endpoint as regional or distant metastasis, but regional progression data was not collected.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Percentage of Participants With General Clinical Treatment Failure', 'description': 'General clinical treatment failure (GCTF) is defined as: PSA \\> 25 ng/ml, documented local disease progression, regional or distant metastasis, or initiation of salvage androgen deprivation therapy. Failure time is defined as time from registration to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Percentage of Participants With Death Due to Prostate Cancer', 'description': 'Time to prostate cancer death is defined as time from randomization to the date of death due to prostate cancer, last known follow-up (censored), or death due to other causes (competing risk). Failure rates were to be estimated using the cumulative incidence method. If too few events occur for meaningful estimates, then only counts of events will be reported.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year', 'description': 'The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year.', 'timeFrame': 'Baseline, one year'}, {'measure': 'Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year', 'description': 'The EPIC-Short Form is a 26-item, validated self-administered tool to assess disease-specific aspects of prostate cancer and its therapies consisting of five summary domains (bowel, urinary incontinence, urinary irritation/obstruction, sexual, and hormonal function). Responses for each item form a Likert scale which are transformed to a 0-100 scale. A domain score is the average of the transformed domain item scores, ranging from 0-100 with higher scores representing better health-related quality of life (HRQOL). Change at one year is defined as one-year value - baseline value. Positive change at one year indicates improved quality of life.', 'timeFrame': 'Baseline, one year'}, {'measure': 'Serum Testosterone', 'timeFrame': 'Baseline,12 months, 24 months'}, {'measure': 'Fasting Total Cholesterol', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Serum High-density Lipoprotein (HDL)', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Serum High-density Lipoprotein (LDL)', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Hemoglobin A1c', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Fasting Plasma Glucose', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Fasting Plasma Insulin', 'timeFrame': 'Baseline, 12 months, 24 months'}, {'measure': 'Change From Baseline in Body Mass Index (BMI)', 'description': "Body Mass Index (BMI) is a person's weight in kilograms (or pounds) divided by the square of height in meters (or feet). Change from baseline = time point value - baseline value.", 'timeFrame': 'Baseline and yearly to five years.'}, {'measure': 'Number of Participants by Highest Grade Adverse Event', 'description': 'Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data', 'timeFrame': 'From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Testosterone Recovery at 12 and 24 Months', 'description': 'Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Time to testosterone recovery is defined as time from randomization to the date of testosterone recovery, biochemical, local, or distant failure (competing risk), salvage therapy (competing risk), death (competing risk), or last known follow-up (censored). Testosterone recovery rates are estimated using the cumulative incidence method.', 'timeFrame': 'From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years.'}, {'measure': 'Median Testosterone Recovery Time', 'description': 'Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Testosterone recovery rates are estimated using the Kaplan-Meier method, censoring for biochemical, local, or distant failure, salvage therapy, death, and otherwise alive without event. Testosterone recovery time is defined as time from randomization to testosterone recovery or censoring.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}, {'measure': 'Number of Patients With Clinical Survivorship Events', 'description': 'Clinical survivorship events are defined as the following newly diagnosed non-fatal cardiovascular events or other clinical endpoints relevant to prostate cancer survivorship:\n\ntype 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and osteoporotic fracture.', 'timeFrame': 'From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.'}] |
Title: A Randomized Prospective Clinical Trial to Evaluate Efficacy and Safety of LACUDY for Improving Vaginal Environment Among Breast Cancer Survivals Who Receive Anti-estrogen Therapy | Condition: Hormone Receptor-positive Breast Cancer | Keywords: | Summary: | Description: * Registered subjects are 1:1 randomized using a random sequencing generator (www.random.org). Experimental group with 30 patients and Control group with 30 patinets.
* In the case of the experimental group, LACUDY 2mL is inserted twice a week for a month before going to bed for 4 weeks.
* Unpack the product and take it out.
* Remove the cap by turning it.
* Fit the nozzle to the end of the syringe and turn it to combine.
* Hold the syringe with the nozzle facing the vulva, insert it about 5-6 cm into the vagina, and then slowly press the tip of the push rod with patient's thumb to inject all the liquid in the syringe into the vagina.
* Slowly remove the syringe as the nozzle opens.
* It is recommended to wear a pad as the injected solution may flow out.
* In the case of the control group, they go about their daily lives without any treatment.
* Both the experimental group and the control group are instructed not to administer intravaginal suppositories or other drugs related to vaginal atrophy and sexual function improvement.
* A total of 2 questionnaires were conducted before and after treatment. | ArmGroups: [{'label': 'Experimental', 'type': 'EXPERIMENTAL', 'description': 'Breast cancer patient who treated with LACUD', 'interventionNames': ['Drug: LACUDY']}, {'label': 'Observation', 'type': 'NO_INTERVENTION', 'description': 'Breast cancer patient who does not treated with LACUD'}] | Interventions:[{'type': 'DRUG', 'name': 'LACUDY', 'description': 'LACUDY:Insert 2mL twice a week for 4 weeks before going to bed', 'armGroupLabels': ['Experimental'], 'otherNames': ['IC-LC02S2Q2']}] | PrimaryOutcomes: [{'measure': 'Change of Vaginal health index', 'description': 'Female Sexual Function Index (FSFI) Quality of life assessed by Breast Version 4 (FACT-B)', 'timeFrame': 'Prior to administration, 1 month after LacuD treatment(2 times in total)'}] | SecondaryOutcomes: [{'measure': 'Vaginal microbiome', 'description': 'Take one cervicovaginal swab sample each', 'timeFrame': 'Prior to administration, 1 month after LacuD treatment(2 times in total)'}] |
Title: Effect of Intravenous Infusion of Lidocaine on Patients Undergoing Radical Resection of Colorectal Tumors | Condition: Colorectal Tumors, Lidocaine | Keywords: Radical resection of colorectal tumor, lidocaine, stress, immunity, vascular tumor regeneration, inflammation, micrometastasis | Summary: | Description: Lidocaine was applied in the operation of colorectal tumor patients, and the effect on the postoperative microenvironment and micrometastasis of the patients was observed by detecting the stress, immunity, vascular tumor regeneration, inflammation, etc. of the patients. | ArmGroups: [{'label': 'Lidocaine is used in radical resection of colorectal tumors.', 'type': 'EXPERIMENTAL', 'description': 'Administer 1.5 mg/kg intravenously to the patient before induction of anesthesia, and continue to infuse 1.5 mg/kg/h during the operation until the end of the operation', 'interventionNames': ['Drug: Administer 1.5 mg/kg intravenously to the patient before induction of anesthesia, and continue to infuse 1.5 mg/kg/h during the operation until the end of the operation']}] | Interventions:[{'type': 'DRUG', 'name': 'Administer 1.5 mg/kg intravenously to the patient before induction of anesthesia, and continue to infuse 1.5 mg/kg/h during the operation until the end of the operation', 'description': 'Administer 1.5 mg/kg lidocaine', 'armGroupLabels': ['Lidocaine is used in radical resection of colorectal tumors.'], 'otherNames': ['same volume of saline']}] | PrimaryOutcomes: [{'measure': 'the concentration of tumor micrometastasis markers were determined by ELISA', 'description': 'the concentration of tumor micrometastasis markers such as CK20 was determined by ELISA', 'timeFrame': '3 days after surgery'}] | SecondaryOutcomes: [{'measure': 'the concentration of stress hormones were determined by ELISA', 'description': 'the concentration of EPI and NE were determined by ELISA', 'timeFrame': '3 days after surgery'}, {'measure': 'the concentration of inflammatory factor were determined by ELISA', 'description': 'the concentration of IL-6,IL-8,TNF-α were determined by ELISA', 'timeFrame': '3 days after surgery'}, {'measure': 'the concentration of angiogenesis factors were determined by ELISA', 'description': 'the concentration of VEGF was determined by ELISA', 'timeFrame': '3 days after surgery'}, {'measure': 'the concentration of immune indexes were determined by ELISA', 'description': 'the concentration of B lymphocytes, T lymphocytes, NK cells, macrophages were determined by ELISA', 'timeFrame': '3 days after surgery'}] |
Title: Phase 1a/1b Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells (MC10029) in Subjects With Relapsed or Refractory BAFFR-Expressing B-Cell Hematologic Malignancies | Condition: B-Cell Non-Hodgkin Lymphoma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Recurrent Transformed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Refractory Diffuse Large B-Cell Lymphoma, Refractory Follicular Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Marginal Zone Lymphoma, Refractory Small Lymphocytic Lymphoma, Refractory Transformed Chronic Lymphocytic Leukemia | Keywords: | Summary: | Description: PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of (MC10029) autologous BAFFR-targeting chimeric antigen receptor (CAR) T cells following lymphodepleting (LD) therapy in subjects with relapsed or refractory BAFFR expressing B-cell hematologic malignancies.
II. To determine the recommended dose for phase 1b (dose expansion) and recommend phase 2 dose.
SECONDARY OBJECTIVES:
I. To assess the efficacy and antitumor activity of MC10029 in subjects with relapsed or refractory BAFFR-expressing B-cell hematologic malignancies.
II. To determine long-term toxicities in MC10029 recipients. III. To determine feasibility of manufacturing success rate of MC10029.
CORRELATIVE RESEARCH OBJECTIVES:
I. To evaluate the pharmacokinetics of MC10029 in peripheral blood samples. II. To study the relationship between BAFFR expression and clinical activity of MC10029.
OUTLINE:
Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV), over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and magnetic resonance imaging (MRI) at screening, computed tomography (CT) scan, positron emission tomography (PET) scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression.
After completion of study treatment, patients followed up at day 1, 2, 3, 4, 8, 11, 14, 21, 28, 60, 90, 180, 270, 365, 545 and 730 and then periodically for up to 15 years. | ArmGroups: [{'label': 'Treatment (BARRF based chimeric antigen receptor T-cells)', 'type': 'EXPERIMENTAL', 'description': 'Patients undergo leukapheresis. Patients then receive cyclophosphamide IV, over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and MRI at screening, CT scan, PET scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression.', 'interventionNames': ['Biological: Autologous BAFFR-targeting CAR T Cells', 'Drug: Bendamustine', 'Procedure: Biopsy', 'Procedure: Biospecimen Collection', 'Procedure: Bone Marrow Aspiration and Biopsy', 'Procedure: Computed Tomography', 'Drug: Cyclophosphamide', 'Procedure: Echocardiography', 'Drug: Fludarabine', 'Procedure: Leukapheresis', 'Procedure: Magnetic Resonance Imaging', 'Procedure: Positron Emission Tomography']}] | Interventions:[{'type': 'BIOLOGICAL', 'name': 'Autologous BAFFR-targeting CAR T Cells', 'description': 'Given IV', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Autologous BAFFR-CAR T Cells', 'Autologous BAFFR-CAR-expressing T-cells']}, {'type': 'DRUG', 'name': 'Bendamustine', 'description': 'Given IV', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['SDX-105']}, {'type': 'PROCEDURE', 'name': 'Biopsy', 'description': 'Undergo biopsy', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['BIOPSY_TYPE', 'Bx']}, {'type': 'PROCEDURE', 'name': 'Biospecimen Collection', 'description': 'Undergo blood sample collection', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Biological Sample Collection', 'Biospecimen Collected', 'Specimen Collection']}, {'type': 'PROCEDURE', 'name': 'Bone Marrow Aspiration and Biopsy', 'description': 'Undergo bone marrow biopsy/aspirate', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)']}, {'type': 'PROCEDURE', 'name': 'Computed Tomography', 'description': 'Undergo CT scan', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['CAT', 'CAT Scan', 'Computed Axial Tomography', 'Computerized Axial Tomography', 'Computerized axial tomography (procedure)', 'Computerized Tomography', 'CT', 'CT Scan', 'tomography']}, {'type': 'DRUG', 'name': 'Cyclophosphamide', 'description': 'Given IV', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['(-)-Cyclophosphamide', '2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate', 'Asta B 518', 'B-518', 'Carloxan', 'Ciclofosfamida', 'Ciclofosfamide', 'Cicloxal', 'Clafen', 'Claphene', 'CP monohydrate', 'CTX', 'CYCLO-cell', 'Cycloblastin', 'Cycloblastine', 'Cyclophospham', 'Cyclophosphamid monohydrate', 'Cyclophosphamide Monohydrate', 'Cyclophosphamidum', 'Cyclophosphan', 'Cyclophosphane', 'Cyclophosphanum', 'Cyclostin', 'Cyclostine', 'Cytophosphan', 'Cytophosphane', 'Cytoxan', 'Fosfaseron', 'Genoxal', 'Genuxal', 'Ledoxina', 'Mitoxan', 'Neosar', 'Revimmune', 'Syklofosfamid', 'WR- 138719', 'WR-138719']}, {'type': 'PROCEDURE', 'name': 'Echocardiography', 'description': 'Undergo echocardiography', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['EC']}, {'type': 'DRUG', 'name': 'Fludarabine', 'description': 'Given IV', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Fluradosa']}, {'type': 'PROCEDURE', 'name': 'Leukapheresis', 'description': 'Undergo leukapheresis', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Leukocytopheresis', 'Therapeutic Leukopheresis']}, {'type': 'PROCEDURE', 'name': 'Magnetic Resonance Imaging', 'description': 'Undergo MRI', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Magnetic Resonance', 'Magnetic resonance imaging (procedure)', 'Magnetic Resonance Imaging Scan', 'Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance', 'MR', 'MR Imaging', 'MRI', 'MRI Scan', 'MRIs', 'NMR Imaging', 'NMRI', 'Nuclear Magnetic Resonance Imaging', 'sMRI', 'Structural MRI']}, {'type': 'PROCEDURE', 'name': 'Positron Emission Tomography', 'description': 'Undergo PET scan', 'armGroupLabels': ['Treatment (BARRF based chimeric antigen receptor T-cells)'], 'otherNames': ['Medical Imaging, Positron Emission Tomography', 'PET', 'PET Scan', 'Positron emission tomography (procedure)', 'Positron Emission Tomography Scan', 'Positron-Emission Tomography', 'proton magnetic resonance spectroscopic imaging', 'PT']}] | PrimaryOutcomes: [{'measure': 'Incidence of dose-limiting toxicities (DLT)', 'description': 'DLTs are defined per the protocol and assessed by the number of DLTs that occur during the DLT evaluation period and persist beyond the specified duration (relative to the time of onset, defined as within 28 days).', 'timeFrame': 'Up to 28 days after MC10029 (autologous B-cell activating factor receptor [BAFFR]-targeting chimeric antigen receptor [CAR] T cells product) infusion'}, {'measure': 'Incidence and severity of treatment emergent adverse events', 'description': 'Defined as adverse events (AEs) that occur or worsen in severity on or after MC10029 product infusion.', 'timeFrame': 'Up to 15 years'}] | SecondaryOutcomes: [{'measure': 'Overall response rate', 'description': 'Will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) by the positron emission tomography-computed tomography (PET-CT) based response criteria . Will be assessed according to Lugano criteria for lymphomas (follicular lymphoma \\[FL\\], mantle cell lymphoma \\[MCL\\], marginal zone lymphoma \\[MZL\\], large b-cell lymphoma \\[LBCL\\]) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria for chronic lymphocytic leukemia (CLL).', 'timeFrame': 'Up to 15 years'}, {'measure': 'Complete response rate', 'description': 'Will be assessed according to Lugano criteria for lymphomas (FL, MCL, MZL, LBCL) and iwCLL 2018 criteria for CLL.', 'timeFrame': 'Up to 15 years'}, {'measure': 'Duration of response', 'description': 'Defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.', 'timeFrame': 'Up to 15 years'}, {'measure': 'Progression free survival', 'description': 'Defined as the time from initiation of treatment to the occurrence of disease progression or death.', 'timeFrame': 'Up to 15 years'}, {'measure': 'Overall survival', 'description': 'Defined as the time from treatment to death, regardless of disease recurrence.', 'timeFrame': 'Up to 15 years'}, {'measure': 'Number of conforming versus nonconforming products', 'description': 'Will be noted and reported. A conforming cell product product must have met all release criteria for infusion. No patient will receive a non-conforming product under this protocol, thus this endpoint will be evaluated by the Quality Assurance/Quality Control team.', 'timeFrame': 'Up to 15 years'}] |
Title: Imaging Tumor-infiltrating CD8+ T-cells in Non-small Cell Lung Cancer Upon Neo-adjuvant Treatment With Durvalumab (MEDI4736) | Condition: Non-small Cell Lung Cancer | Keywords: | Summary: | Description: This is an interventional study in 20 patients with resectable non-small cell lung cancer who will receive 2 courses of durvalumab (MEDI4736) in the neo-adjuvant setting, followed by surgery with curative intent.
Experimental imaging procedures include 1) Zr-89-labelled durvalumab (MEDI4736) scan prior to neo-adjuvant treatment to determine accessibility and intra-tumoral distribution of durvalumab (MEDI4736) and 2) (first cohort) injection of ex vivo \[111In\]-oxine labelled autologous CD8+ T-cells 48 hours prior to surgery, or (second cohort) injection of \[89Zr\]-Df-crefmirlimab prior to surgery. The scan is scheduled on the day of surgery and after surgery, the resected tumor specimen with ex vivo \[111In\]-oxine labelled or in vivo \[89Zr\]-Df-crefmirlimab labelled CD8+ T-cells in situ, is fixated for high-resolution ex vivo imaging on a preclinical U-SPECT scanner and quantitative histopathological analysis, next to standard histopathological evaluation.
Total duration of the study is maximum 42 days (from injection therapeutic dose durvalumab (MEDI4736) to surgery). | ArmGroups: [{'label': 'Durvalumab (MEDI4736) neo-adjuvant', 'type': 'EXPERIMENTAL', 'description': 'Patients will receive two courses of durvalumab (MEDI4736)at a fixed dose of 750mg Q2W intravenously, prior to scheduled resection of NSCLC. Patients are amendable to adjuvant chemo and/or radiation treatment, per standard-of-care. Additionally, patients will undergo a Zr-89 labelled durvalumab (MEDI4736) PET/CT and dedicated perfusion-CT prior to treatment with durvalumab (MEDI4736) and ex vivo In-111-oxine or in vivo \\[89Zr\\]-Df-crefmirlimab labelled CD8+ T-cells after two courses of treatment, prior to surgery.', 'interventionNames': ['Radiation: Zr-89 labelled durvalumab PET/CT', 'Drug: Durvalumab (MEDI4736)']}] | Interventions:[{'type': 'RADIATION', 'name': 'Zr-89 labelled durvalumab PET/CT', 'description': 'Patients will undergo a Zr-89 labelled durvalumab (MEDI4736) PET/CT and dedicated perfusion-CT prior to treatment with durvalumab (MEDI4736) and in- and ex-vivo In-111-oxine or in-vivo \\[89zr\\]-Df-crefmirlimab labelled CD8+ T-cells after two courses of treatment, prior to surgery.', 'armGroupLabels': ['Durvalumab (MEDI4736) neo-adjuvant'], 'otherNames': ['In-111-oxine labelled CD8+ T-cell scintigraphy OR [89Zr]-Df-crefmirlimab PET', 'Dedicated perfusion-CT']}, {'type': 'DRUG', 'name': 'Durvalumab (MEDI4736)', 'description': 'Patients will receive two courses of durvalumab (MEDI4736)at a fixed dose of 750mg Q2W intravenously, prior to scheduled resection of NSCLC.', 'armGroupLabels': ['Durvalumab (MEDI4736) neo-adjuvant']}] | PrimaryOutcomes: [{'measure': 'Safety of neo-adjuvant durvalumab: number of NCI CTCAE v 5.0 grade ≥3', 'description': 'Demonstrate safety of two courses durvalumab (MEDI4736) 750 mg at two weeks interval in neo-adjuvant setting. Safety is defined as the number of NCI CTCAE v 5.0 grade ≥3 toxicity related to neo-adjuvant durvalumab (MEDI4736).', 'timeFrame': '14 days'}, {'measure': 'Feasibility of neo-adjuvant durvalumab: successful completion of curative surgery', 'description': 'Demonstrate feasibility of two courses durvalumab (MEDI4736) 750 mg at two weeks interval in neo-adjuvant setting. Feasibility is defined as successful completion of curative surgery within 42 days after start of neo-adjuvant treatment with durvalumab (MEDI4736) (= day 1).', 'timeFrame': '42 days'}] | SecondaryOutcomes: [{'measure': 'Imaging related_response on CE-CT', 'description': 'Objective responses measured on contrast enhanced CT (RECIST1.1, immune related response criteria (irRC))', 'timeFrame': '42 days'}, {'measure': 'Imaging related_pathological response', 'description': 'The rate of (major and complete) pathological responses as previously defined.', 'timeFrame': '42 days'}, {'measure': 'Imaging related_correlation with Zr89-labelled durvalumab', 'description': 'Correlate the presence and localisation of TILs with the intra-tumoral distribution of Zr-89-labelled durvalumab (MEDI4736).', 'timeFrame': '42 days'}, {'measure': 'Imaging related_correlation with perfusion-CT', 'description': 'Correlate the presence and localisation of TILs and Zr-89-labelled durvalumab (MEDI4736) with (changes in) perfusion parameters on contrast-enhanced CT.', 'timeFrame': '42 days'}, {'measure': 'Biomarker related_future correlation with other biomarkers', 'description': 'Exploration of In-111-oxine or \\[89Zr\\]-Df-crefmirlimab labelled T-cells U-SPECT or PET findings with other potential biomarkers (not yet defined) for response to immune therapy and the number of immune therapy related conversions from VATS to open surgical procedures', 'timeFrame': '42 days'}, {'measure': 'Biomarker related_correlation with immune profiling', 'description': 'Correlate the presence of TILs with multi-dimensional immune profiling by flow cytometry of freshly isolated peripheral blood lymphocytes.', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_evaluation of VATS conversions', 'description': 'Evaluate the number of VATS conversions after neo-adjuvant durvalumab (MEDI4736).', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_number of patients with postoperative complications', 'description': 'Asses postoperative complications', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_hospital stay', 'description': 'Asses length of hospital stay', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_mortality', 'description': 'Asses 30 and 90 day mortality', 'timeFrame': '30 and 90 days'}, {'measure': 'Clinical care related_evaluation of patient related outcomes', 'description': 'Patient related outcome measurements (PROMS) will be evaluated based on the EORTC-QLQ-C30 (quality of life) questionnaire (in Dutch) at baseline, prior to surgery, at first post-operative visit and follow-up.\n\nThe QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.\n\nThus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_determination of recurrence-free survival', 'description': 'Determine recurrence-free survival by landmarking analysis, based on time since surgery.', 'timeFrame': '42 days'}, {'measure': 'Clinical care related_determination of overall survival', 'description': 'Determine overall survival by landmarking analysis, based on time since surgery.', 'timeFrame': '42 days'}] |
Title: A Phase II Study of Algenpantucel-L (HyperAcute Pancreas) Cancer Vaccine in Subjects With Surgically Resected Pancreatic Cancer | Condition: Pancreatic Cancer | Keywords: pancreatic cancer, vaccine | Summary: | Description: Unfortunately, despite the best clinical efforts and breakthroughs in biotechnology, most patients diagnosed with pancreatic cancer continue to die from their disease in a very short period of time. The primary reason for this is the short progression time of the disease; in fact, most patients with pancreatic cancer have symptoms at the time of the diagnosis. Moreover, lack of any single agent or procedure to have any significant impact on long term survival rates further contributes to poor prognostic outcomes observed with this disease.
These reasons are the major causes of cancer progression that are usually discussed when considering treatment options for patients with disease that continues to grow and spread. However, another important part of the body should be considered-- the immune system. Scientists have clearly shown that pancreatic cancer cells as well as other cancer cells produce a number of abnormal proteins or abnormal amounts of certain proteins not found in normal cells. Normally one would expect a patient to develop an immune response against these abnormal proteins found in their cancer and attack them much the way we would fight off an infection from a foreign bacteria or virus. However, for reasons that scientists do not fully understand, the immune system fails to respond to these abnormal proteins and does not attack the cancer cells. This human clinical trial proposes a new way to make the immune system recognize the cancer and encourage it to attack the cancer cells.
Many people are familiar with the idea of transplants between people of organs like the kidneys or heart. When an organ transplant between two people is completed one of the problems that can occur is rejection of the donated organ by the recipient. This can occur because the immune system of the patient who receives the organ attacks the donated organ. If you were to attempt to transplant a pig heart to a human the rejection would be dramatically stronger than when organs are transplanted between two people. This is partly because lower animals express sugar-protein patterns on the surface of their cells that humans do not. In fact, our immune systems can quickly recognize tissues from lower mammals such as the pig or the mouse and destroys them.
In this project, we propose to put a mouse gene into human pancreatic cancer cells that produces these abnormal sugar patterns and stimulates the immune system to attack the pancreatic cancer. This strategy works well to kill other human cancer cells in the laboratory, but it needs to be tried in pancreatic cancer patients to see if it will be effective. We propose to test this new treatment in patients with pancreatic cancer who have undergone tumor resection to see if it can stop or slow recurrence of tumors in these patients. Patients will be injected with an anti-tumor vaccine consisting of a mixture of two types of dead human pancreatic cancer cells that have been genetically altered to express the mouse gene responsible for making this abnormal sugar-protein on the cells. | ArmGroups: [{'label': 'Vaccine group', 'type': 'EXPERIMENTAL', 'interventionNames': ['Biological: HyperAcute(R)-Pancreatic Cancer Vaccine']}] | Interventions:[{'type': 'BIOLOGICAL', 'name': 'HyperAcute(R)-Pancreatic Cancer Vaccine', 'description': '100 million vaccine cells will be injected intradermally for up to 14 vaccinations over approximately 8 months', 'armGroupLabels': ['Vaccine group'], 'otherNames': ['HAPa-1 and HAPa-2 vaccine components']}] | PrimaryOutcomes: [{'measure': 'The primary objective of this Phase II trial is to assess disease-free survival (DFS) at one (1) year following initiation of treatment as the primary endpoint of the study in subjects treated with the HyperAcute®-Pancreatic Cancer Vaccine', 'timeFrame': 'one year'}] | SecondaryOutcomes: [{'measure': 'We will use overall survival and adverse events rates as secondary endpoints.', 'timeFrame': 'Duration of study'}] |
Title: Phase I/II Study of Intravenous Ascorbic Acid in Treatment of Metastatic Hepatocellular Carcinoma | Condition: Metastatic Hepatocellular Carcinoma, Advanced Liver Cancer | Keywords: Vitamins, Malignant Tumor, Tumour, Integrative Medicine, Complementary Medicine, Alternative Medicine Antioxidants, Molecular Mechanisms of Pharmacological Action, Pharmacologic Actions, Protective Agents, Physiological Effects of Drugs, Micronutrients, Growth Substances, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Therapeutic Uses, Radiation-Sensitizing Agents, Liver Cancer | Summary: | Description: Intravenous Ascorbic Acid (Vitamin C) is a widely used alternative cancer treatment. This trial will study an intravenous Vitamin C treatment for persons with liver cancer that has spread, who are also receiving Sorafenib (a standard cancer drug), to see whether the combination of Vitamin C and Sorafenib is safe and well tolerated. Phase I will involve 6 persons who will receive the Vitamin C for 8 weeks to more specifically assess the safety of getting Vitamin C in combination with Sorafenib. Phase II will be randomized to receive either Vitamin C plus Sorafenib or Sorafenib alone for 16 weeks. If Vitamin C has a beneficial effect on tumour cells, patients may experience a regression of tumor or tumor markers. Additional benefits include scans at no charge to the patient. | ArmGroups: [{'label': 'Ascorbic Acid + Sorafenib', 'type': 'EXPERIMENTAL', 'description': 'Drug: Vitamin C Other Names: Ascorbic Acid, Ascorbate\n\nDosage:\n\nVitamin C : 100 grams (infusion) Phase I: 3x a week for 8 weeks Phase II: 3x a week for 16 weeks Sorafenib: taken daily (oral)', 'interventionNames': ['Drug: Ascorbic Acid + Sorafenib']}, {'label': 'Sorafenib alone', 'type': 'OTHER', 'description': 'Sorafenib: taken daily (oral)', 'interventionNames': ['Drug: Sorafenib']}] | Interventions:[{'type': 'DRUG', 'name': 'Ascorbic Acid + Sorafenib', 'armGroupLabels': ['Ascorbic Acid + Sorafenib'], 'otherNames': ['Vitamin C', 'Ascorbate']}, {'type': 'DRUG', 'name': 'Sorafenib', 'armGroupLabels': ['Sorafenib alone'], 'otherNames': ['Nexavar']}] | PrimaryOutcomes: [{'measure': 'Number of Participants That Experience Serious Adverse Events.', 'description': 'The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with sorafenib therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE)v4.0', 'timeFrame': '16 weeks +/- 2 weeks'}] | SecondaryOutcomes: [{'measure': 'Overall Tumor Response Rate', 'description': 'To utilize CT or PET/CT scans to assess overall tumor response rate (complete) in subjects with advanced metastatic hepatocellular cancer treated with the combination of ascorbic acid and sorafenib versus sorafenib alone.', 'timeFrame': '16 weeks +/- 2 weeks'}, {'measure': 'Mean Value Collected Using the Functional Assessment of Cancer Therapy-General (FACT-G) Quality Assessment Instrument', 'description': 'To evaluate quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) quality assessment instrument. The FACT-G questionnaire will be used to assess quality-of-life longitudinally. Quality-of-life scores obtained from the FACT-G will be summarized at multiple time points. Five-point scale from 0 (not at all) to 4 (very much)', 'timeFrame': '16 weeks +/- 2 weeks'}, {'measure': 'Number of Participants That Are Alive After 15 Weeks of Treatment.', 'description': 'To evaluate duration of tumor response and progression-free survival', 'timeFrame': '15 weeks+'}] |
Title: A Phase 1/2a, Open-Label, Dose Escalation and Expansion Study of the Safety and Tolerability of T3011 Administered Via Intratumoral Injection as a Single Agent and in Combination With Intravenous Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors | Condition: Solid Tumor, Melanoma, HNSCC, Sarcoma, Squamous Cell Carcinoma, NSCLC | Keywords: | Summary: | Description: This is a Phase 1/2a, open-label, first-in-human study of T3011 given via intratumoral (IT) injection as a single agent and in combination with IV pembrolizumab in participants with advanced or metastatic solid tumors. The Phase 1 portion of the study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of T3011. Total enrollment will depend on the toxicities and/or activity observed, with approximately 15 to 30 evaluable participants enrolled. Once the RP2D is established Phase 2a Part 1 will enroll approximately 10 participants with locally recurrent or metastatic melanoma (in Arm A) 23 to 53 participants with HNSCC in Arm B, 40 to 80 participants with sarcoma in Arm C and 10 participants with cSCC in Arm D. During Phase 2a Part 1 the safety, tolerability, and preliminary efficacy of T3011 as a single agent will be evaluated. Phase 2a Part 2 will enroll in parallel to Phase 2a Part 1 once the RP2D is established. The safety, tolerability, and preliminary efficacy of IT T3011 given in combination with IV pembrolizumab will be evaluated in 15 participants with histologically or pathologically confirmed metastatic NSCLC (Arm E). A rollover arm is also included in this study to allow participants who have documented progression on T3011 alone to receive T3011 in combination with pembrolizumab if considered eligible. | ArmGroups: [{'label': 'Phase 1', 'type': 'EXPERIMENTAL', 'description': 'T3011 single agent dose escalation in participants with solid tumors', 'interventionNames': ['Biological: T3011']}, {'label': 'Phase 2a Part 1 Arm A', 'type': 'EXPERIMENTAL', 'description': 'RP2D T3011 single agent in participants with melanoma', 'interventionNames': ['Biological: T3011']}, {'label': 'Phase 2a Part 1 Arm B', 'type': 'EXPERIMENTAL', 'description': 'RP2D T3011 single agent in participants with other solid tumors', 'interventionNames': ['Biological: T3011']}, {'label': 'Phase 2a Part 2 Arm C', 'type': 'EXPERIMENTAL', 'description': 'RP2D T3011 + pembrolizumab in participants with NSCLC', 'interventionNames': ['Combination Product: T3011 + pembrolizumab']}, {'label': 'Rollover Arm', 'type': 'EXPERIMENTAL', 'description': 'RP2D T3011 + pembrolizumab in participants who have progressed on T3011 single agent', 'interventionNames': ['Combination Product: T3011 + pembrolizumab']}] | Interventions:[{'type': 'BIOLOGICAL', 'name': 'T3011', 'description': 'T3011 will be administered up to 4mL as an intratumoral injection given Q2W.', 'armGroupLabels': ['Phase 1', 'Phase 2a Part 1 Arm A', 'Phase 2a Part 1 Arm B']}, {'type': 'COMBINATION_PRODUCT', 'name': 'T3011 + pembrolizumab', 'description': 'T3011 will be administered up to 4mL as an intratumoral injection in combination with intravenous pembrolizumab given Q3W.', 'armGroupLabels': ['Phase 2a Part 2 Arm C', 'Rollover Arm']}] | PrimaryOutcomes: [{'measure': 'Safety and tolerability of escalating doses T3011', 'description': 'Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'To determine the dose(s) of T3011 to be examined in Phase 2a', 'description': 'Incidence of DLTs', 'timeFrame': 'Through the first two T3011 injections (approximately 28 days)'}, {'measure': 'Safety and tolerability of T3011 dose(s) selected from Phase 1 in disease specific cohorts', 'description': 'Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Characterize the safety and tolerability of T3011 in combination with pembrolizumab', 'description': 'Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Characterize the safety and tolerability of T3011 in combination with pembrolizumab in participants who progress on T3011 alone', 'description': 'Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.', 'timeFrame': 'Up to 2 years from first dose of T3011'}] | SecondaryOutcomes: [{'measure': 'Overall response rate (ORR)', 'description': 'ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments by RECIST v1.1 and iRECIST.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Disease control rate (DCR)', 'description': 'DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments by RECIST v1.1 and iRECIST.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Duration of response (DOR)', 'description': 'DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Durable response (DR)', 'description': 'DR is defined as objective response (CR or PR) according to RECIST v1.1 and iRECIST.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Progression-free survival (PFS)', 'description': 'PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST v1.1 and iRECIST.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Overall Survival (OS)', 'description': 'OS is defined as the time from enrollment to death from any cause.', 'timeFrame': 'Up to 1 year after last dose of T3011'}, {'measure': 'Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development', 'description': 'To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 given as single agent and in combination with pembrolizumab post injection.', 'timeFrame': 'Up to 2 years from first dose of T3011'}, {'measure': 'Presence and frequency of T3011 in injection site swab, saliva, and urine', 'description': 'To evaluate the virus shedding of T3011 following intratumoral injection', 'timeFrame': 'Up to 2 years from first dose of T3011'}] |
Title: Understanding the Post-Surgical Non-Small Cell Lung Cancer Patient's Symptom Experience | Condition: Lung Cancer | Keywords: Lung Cancer, Symptoms | Summary: | Description: Study Procedures:
Participants will be randomly assigned (like flipping a coin) to one of the following groups upon completion of collection of initial information about the participant's: current and prior health history, symptoms, and health-related quality of life, and take a 6-minute self-paced walking test to measure walking ability. This test will occur at Spectrum Health facility before surgery.
Groups: 1) The Symptom Experience Group and the 2) Light Physical Activity Group
Description of the Symptom Experience Group:
In addition to receiving conventional treatment for your cancer, as prescribed by your health care providers, you will receive planned, structured, weekly telephone visits to report the experience of your symptoms and health-related quality of life questions.
In the Symptom Experience Group you will:
* Provide information about your current and prior health history.
* Take a 6-minute self-paced walking test to measure your walking ability at Spectrum Health facility before surgery and at approximately 6-weeks after returning home from the hospital (prior to possible chemotherapy and/or radiation therapy).
* Wear a pedometer each day of the study and record the number of steps you take each day.
* Contact the nurse researcher if you have any study related questions.
* Record information and comments in a daily diary (takes approximately 2 minutes to complete each day) and answer research questions via a weekly telephone visit throughout the study.
If you wish to take part in this study you will need to:
* Keep your study appointments.
* Tell your telephone research assistant about any medications you are taking.
* Tell your telephone research assistant about any side effects, doctor visits, or hospitalizations that you may have whether or not you think they are related to the study.
In the Symptom Experience Group you will receive:
* Program education prior to surgery.
* A telephone visit within 3 days (24 hours is optimum) after being discharged from the hospital to ask questions about your health with the interview taking approximately 30 minutes.
* The health interview can be rescheduled for completion within 3 days of hospital discharge should you not feel well enough to complete the interview.
* At the end of weeks 1-6, we will make a telephone visit to complete health questionnaires with most interviews taking 15 minutes except on weeks 3 and 6 taking approximately 30 minutes.
* Upon completion of your participation in the Symptom Experience Group, you will receive information regarding the light physical activity program.
* Upon completion of the study, you will be provided an overview of the results of the study.
Description of the Light Physical Activity Group:
In addition to receiving conventional treatment for cancer, as prescribed by your health care providers, you will receive a home-based light physical activity program to help you manage a specific symptom related to cancer and cancer treatment.
In the Light Physical Activity Group you will:
* Provide information about your current and prior health history.
* Take a 6-minute self-paced walking test to measure your walking ability at a Spectrum Health facility before surgery and at approximately 6-weeks after returning home from the hospital (prior to possible chemotherapy and/or radiation therapy).
* Participate in a self-scheduled, home-based physical activity program to help you learn how to manage a specific symptom related to cancer and cancer treatment for a total of six weeks following your return home from the hospital.
* Participate in a time commitment starting at 5 minutes a day 5 days a week gradually increasing to 30 minutes a day 5 days a week as able by week 6.
* Wear a pedometer each day of the study and record the number of steps you take each day.
* Record information and comments in a daily diary (takes approximately 2 minutes to complete each day) and answer research questions via a weekly telephone visit throughout the study.
* Contact the nurse researcher if you have any study related questions. If you wish to take part in this study you will need to:
* Keep your study appointments.
* Tell your nurse about any medications you are taking.
* Tell your nurse about any side effects, doctor visits, or hospitalizations that you may have whether or not you think they are related to the study.
In the Light Physical Activity Group you will receive:
* Program education prior to surgery.
* A telephone visit from a nurse within 3 days (24 hours is optimum) after being discharged from the hospital to:
* Ask questions about your symptoms to see if you are ready to start light physical activity program taking approximately 5 minutes.
* If you are ready, we will arrange a home visit within 4 days of discharge.
* If not ready, we will contact your surgeon to help you and call you each day to assess if you are ready to start.
* A telephone visit from a research assistant within 3 days (24 hours is optimum) after being discharged from the hospital to:
* Ask questions about your health with the interview taking approximately 30 minutes.
* The health interview can be rescheduled for completion within 3 days of hospital discharge should you not feel well enough to complete the interview.
* The first home visit from the nurse after surgery will take approximately 2 hours and the nurse will:
* Assemble and teach you how to operate the physical activity equipment.
* Assist you in completing your first physical activity on this day.
* Follow-up your first home visit with a telephone visit within 24 hours to answer any questions and concerns about the program.
* At the beginning of week two, the nurse will make one more home visit, and at the beginning of weeks 3-6 the nurse will make a telephone visit to collect and review your recorded information.
* The nurse will be available to make additional home and telephone visits should you need assistance.
* At the end of weeks 1-6, research staff will make a telephone visit to complete the health questionnaires with most interviews taking 15 minutes except on weeks 3 and 6 taking approximately 30 minutes.
We expect 86 persons, 21 years of age or older who are scheduled for surgery to treat lung cancer from the west Michigan area to participate in the study.
The potential risks for the Symptom Experience and Light Physical Activity Groups Include:
Risks associated with the six-minute walk test are considered low. The study may involve risks to you which are currently unknown or unforeseeable. Risks may include and are not limited to:
* You may stumble or fall, get short of breath, experience muscle cramps, nausea, chest pain, and abnormal blood pressure.
* The walk test is self-paced by the participant for six-minutes and will be stopped if you want it to be stopped.
The potential risks of this study for the Light Physical activity Group Include:
* The light physical activity program as prescribed in this study corresponds to normal every day activities that are mildly exerting and pose no greater challenge than normal activities of daily living such as:
* Strolling slowly in your home or at work. Grocery shopping.
* Performing light work in the house such as making a bed, washing dishes, preparing food, dusting, and carrying out the trash.
* Riding a lawn mower to mow the lawn or walking applying seed or fertilizer to the lawn.
* Walking in the mall; Bird watching.
* The development or increase of activity-dependent symptoms such as fatigue or muscle or joint soreness.
* The reaction to the body to physical activity cannot always be predicted with accuracy and there is a risk of falling while walking and/or standing in place.
* As part of the program involves the use of your television, some people (1 in 4,000) may have seizures or blackouts triggered by light flashes or patterns while they are watching television or playing such things as video games even if they haven't had a seizure before.
* The reaction of the body to physical activity cannot always be predicted with accuracy so safety procedures are being provided to each participant prior to participation. Safety procedures include but are not limited to:
* Following your physical activity prescription and safety procedures.
* Using tools to monitor your heart rate such as through a heart rate wristwatch monitor.
* Telephone access available during light physical activity.
* Accessing your nurse researchers if you have a concern.
Potential Benefits of the Study:
We cannot promise any benefits to you or others from your taking part in this research. It is hoped that what is learned in this study may benefit other lung cancer patients in the future. If you agree to take part in this study you will receive results of this study in the future following study completion. We will notify you if any significant new findings develop during the course of the study which might affect your willingness to participate.
The potential benefits of being in the Light Physical Activity Group may include:
* Increased ability to manage a symptom related to cancer and its treatment.
* Increased ability in performing day-to-day activities.
* Increased heart and lung (cardiorespiratory) fitness.
* Receiving symptom management help from professional registered nurses.
* Feeling more in control of your symptoms. | ArmGroups: [{'label': 'Symptom Experience Group', 'type': 'ACTIVE_COMPARATOR', 'description': "Conventional treatment for cancer as prescribed by the participant's health care providers and will receive planned, structured, weekly telephone visits to report the experience of symptoms and health-related quality of life information.", 'interventionNames': ['Other: Symptom Experience Report']}, {'label': 'Light Physical Activity Group', 'type': 'EXPERIMENTAL', 'description': "Conventional treatment for cancer as prescribed by the participant's health care providers and will receive a home-based light physical activity program to help manage a specific symptom related to cancer and cancer treatment.", 'interventionNames': ['Behavioral: Light Physical Activity']}] | Interventions:[{'type': 'BEHAVIORAL', 'name': 'Light Physical Activity', 'description': "Conventional treatment for cancer as prescribed by the participant's health care providers and will receive a home-based light physical activity program to help manage a specific symptom related to cancer and cancer treatment.", 'armGroupLabels': ['Light Physical Activity Group']}, {'type': 'OTHER', 'name': 'Symptom Experience Report', 'description': "Conventional treatment for cancer as prescribed by the participant's health care providers and will receive planned, structured, weekly telephone visits to report the experience of symptoms and health-related quality of life information.", 'armGroupLabels': ['Symptom Experience Group']}] | PrimaryOutcomes: [{'measure': 'Determine Feasibility as Measured by Rates of Recruitment.', 'description': 'Rates of recruitment were measured by the percentage of those eligible who enrolled.', 'timeFrame': 'At the beginning of the study.'}, {'measure': 'Feasibility as Measured by Adherence.', 'description': 'Adherence is the percentage of those adhering to the recommended exercise.', 'timeFrame': '6-weeks.'}, {'measure': 'Feasibility as Measured by Retention.', 'description': 'Retention is the percentage of those enrolled and completed and finished the program.', 'timeFrame': '6-weeks.'}, {'measure': 'Feasibility as Measured by Adverse Events.', 'description': "Adverse Events is the percentage of participant's who had an adverse event.", 'timeFrame': '6-weeks.'}] | SecondaryOutcomes: [{'measure': 'Cancer-Related Fatigue Severity', 'description': 'The range of the score was 0 to 10 with 10 meaning the worst cancer-related fatigue and zero meaning no cancer-related fatigue.', 'timeFrame': 'At six weeks after discharge from the hospital after surgery for lung cancer.'}] |
Title: Phase I Study of Afatinib With Postoperative Radiation Therapy for Intermediate and High Risk Squamous Cancer of the Head and Neck (SCCHN) | Condition: Squamous Cell Carcinoma of the Head and Neck | Keywords: | Summary: | Description: If you are willing to take part in this study you will be asked to undergo some screening tests and procedures to confirm your eligibility. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if you do not take part in the research study. If you already had some of these tests and procedures recently, they may or may not have to be repeated. The tests and procedures include: a review of your medical history, physical exam, blood samples, urine sample, serum pregnancy test, electrocardiogram, echocardiogram and an assessment of your disease to find out the extent of your cancer. If these tests show that you are eligible to participate in the research study, you may begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
We will collect an archive tumor specimen (leftover tissue from your prior surgery or biopsies) to confirm your cancer diagnosis. Additional tests on the tumor specimen may be performed as a part of future studies to gain new knowledge about head and neck cancer.
You will receive Afatinib as a pill that you take by mouth for 7 weeks. During the first week, you will receive Afatinib alone. During the second through seventh weeks, you will receive Afatinib together with Radiation Therapy OR with Docetaxel and Radiation Therapy. Docetaxel is given intravenously, once a week during Week 2 through Week 7. Not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they tolerated their doses.
Afatinib needs to be taken on an empty stomach. Specific instructions about this will be included in the drug diary you will need to complete.
If you take part in this research study, you will receive the same radiation that you would receive if you were not on the study. The radiation is typically done daily Monday through Friday for about 6-7 weeks. You will sign a separate consent form with your radiation oncologist that will outline what to expect with this treatment.
You will be given a physical exam every week during your treatment. You will have a physical exam and be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.
You will have blood tests every week during your treatment including chemistry and hematology tests and a pregnancy test if you are a woman capable of becoming pregnant before you receive your first infusion of docetaxel.
You will also be asked to return to the clinic one week, four weeks and eight weeks after finishing your treatment. Most of these visits are part of routine visits after finishing treatment. If you stop the study early for any reason, you will also have a clinic visit. In either instance, the following exams and procedures will be performed: physical exam, blood tests, other tests including an electrocardiogram, MUGA scan or echocardiogram, CT scan and a PET/CT scan. | ArmGroups: [{'label': 'High Risk Group', 'type': 'EXPERIMENTAL', 'description': 'Dose escalation of afatinib + docetaxel + radiation therapy', 'interventionNames': ['Drug: Afatinib', 'Drug: Docetaxel', 'Radiation: Radiation Therapy']}, {'label': 'Intermediate Risk Group', 'type': 'EXPERIMENTAL', 'description': 'Dose escalation of afatinib + radiation therapy', 'interventionNames': ['Drug: Afatinib', 'Radiation: Radiation Therapy']}] | Interventions:[{'type': 'DRUG', 'name': 'Afatinib', 'description': 'Taken orally once per day', 'armGroupLabels': ['High Risk Group', 'Intermediate Risk Group'], 'otherNames': ['Gilotrif']}, {'type': 'DRUG', 'name': 'Docetaxel', 'description': '15 mg/m2, given intravenously once per week', 'armGroupLabels': ['High Risk Group'], 'otherNames': ['Taxotere']}, {'type': 'RADIATION', 'name': 'Radiation Therapy', 'description': 'Daily, Monday-Friday, for six to seven weeks', 'armGroupLabels': ['High Risk Group', 'Intermediate Risk Group']}] | PrimaryOutcomes: [{'measure': 'The presence or absence of a dose-limiting toxicity at a given dose-level of afatinib.', 'description': "All participants who receive any amount of study drug will be evaluable for toxicity. The primary outcome measure is the incidence of a physician-assessed dose-limiting toxicity (DLT) at a given dose-level of afatinib. Participants will be assessed for a DLT at least once per week during the course of therapy, including the one-week afatinib lead-in period and the 6-7 weeks of radiation therapy. DLT's are defined as the incidence of a severe or life-threatening toxicity (grade 3-4) as defined by the Common Terminology Criteria for Adverse Events Versions 4 (CTCAEv.4) or any afatinib-related toxicity requiring a dose reduction occurring during treatment with afatinib and radiation therapy +/- docetaxel. Participants will continue to be assessed for adverse events for 12 weeks after the completion of therapy.", 'timeFrame': '7 weeks'}] | SecondaryOutcomes: N/A |
Title: Adjustment of Optimal Immune System by Using Cytokine Cocktails Before Applying DC Vaccine | Condition: Neoplasms | Keywords: Immunologic Surveillance, Vaccination, Immunotherapy, Dendritic Cells | Summary: | Description: N/A | ArmGroups: [{'label': 'Early (E)', 'type': 'OTHER', 'description': 'Early stage cancer', 'interventionNames': ['Other: Immune profiling and DC vaccine']}, {'label': 'Advanced (A)', 'type': 'OTHER', 'description': 'Advanced stage cancer (Stage IV without treatment)', 'interventionNames': ['Other: Immune profiling and DC vaccine']}, {'label': 'Terminal (T)', 'type': 'OTHER', 'description': 'Terminal stage cancer (Stage IV with chemotherapy)', 'interventionNames': ['Other: Immune profiling and DC vaccine']}] | Interventions:[{'type': 'OTHER', 'name': 'Immune profiling and DC vaccine', 'description': '1. For observational study (immune profiling): blood sampling 3-5 mL\n2. For DC vaccine: one dose of DC vaccine(\\~10 million cells)/2 week for at least 6 month or until progression.', 'armGroupLabels': ['Advanced (A)', 'Early (E)', 'Terminal (T)'], 'otherNames': ['cytokine cocktail']}] | PrimaryOutcomes: [{'measure': 'Immune status', 'timeFrame': '5 years'}] | SecondaryOutcomes: [{'measure': 'Tumor response', 'timeFrame': '6 months'}] |
Title: A Phase II Trial of Calcitriol and Naproxen in Patients With Recurrent Prostate Cancer | Condition: Prostatic Neoplasms, Prostate Cancer | Keywords: | Summary: | Description: In summary, in vitro and in vivo studies, as well as early phase clinical trial, have shown a promising role for both calcitriol and NSAIDs in the treatment of prostate cancer. Moreover, calcitriol and NSAIDs both exert their antiproliferative effect by decreasing prostaglandin levels, but they do so by different mechanisms. Thus, there is reason to believe that their combined effects on prostaglandins may be synergistic. Preliminary in vitro assays in which calcitriol is given in combination with one of two different NSAIDs (Naprosyn or sulindac) to LNCaP cell lines have indicated such synergy. This observation provides the rational for using them in combination for the treatment of prostate cancer. In addition, it is hoped that any synergy noted would allow for the use of lower doses of NSAIDs. | ArmGroups: N/A | Interventions:[{'type': 'DRUG', 'name': 'Calcitriol', 'description': '0.5 micrograms/kilogram q weekly', 'otherNames': ['1,25-Dihydroxycholecalciferol', '1,25-dihydroxyvitamin D3']}, {'type': 'DRUG', 'name': 'Naproxen-n-butyl nitrate', 'description': '400 mg BID, oral', 'otherNames': ['Naprosyn']}] | PrimaryOutcomes: [{'measure': 'PSA response - 50% PSA decline, PSA progression, PSA response duration, progressive disease, time to PSA progression.'}] | SecondaryOutcomes: [{'measure': "Progressive disease in this study's patients, who would be treated with calcitriol and naprosyn, will be compared to that in historical controls of patients treated with calcitriol alone."}] |
Title: A Randomized Controlled Phase III Trial of Treatment Intensification in Stage II-III Colon Cancer Patients With Positive MRD During Adjuvant Chemotherapy | Condition: Colon Cancer | Keywords: Minimal residual disease, Intensified chemotherapy | Summary: | Description: About 25% of resectable high-risk stage 2 or stage 3 colon cancers are known to relapse despite standard treatments, including radical resection and adjuvant chemotherapy.
Using circulating tumor DNA (ctDNA)-based minimal residual cancer (MRD) detection technology, patients whose MRD is not eradicated after adjuvant chemotherapy could be identified. Early introduction of intensified chemotherapy for this group of patients could prolong survival time and increase cure rates.
This study is part of the Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer (CLADIA Colon Cancer). Part 1 of the platform study (Prospective Observational Study of ctDNA Monitoring During Adjuvant) is a large-scale, prospective observational study that follows ctDNA up to three years after resection in about 1,200 patients with stage 2-3 colon cancer.
This study (Part 2) aims to study the efficacy of early intensified chemotherapy (3 months of modified FOLFIRINOX ) compared to standard treatment (FOLFOX/CAPOX for an additional three months to complete six months of standard adjuvant chemotherapy) in patients with stage 2-3 colon cancer in whom ctDNA MRD in the part 1 study remained positive during adjuvant FOLFOX/CAPOX chemotherapy. | ArmGroups: [{'label': 'mFOLFIRINOX intensified chemotherapy', 'type': 'EXPERIMENTAL', 'description': '6 cycles of mFOLFIRINOX\n\n- Modified FOLFIRINOX (mFOLFIRINOX) regimen: 6 cycles every 2 weeks', 'interventionNames': ['Drug: mFOLFIRINOX-FOLFIRI intensified chemotherapy']}, {'label': 'FOLFOX or CAPOX adjuvant chemotherapy', 'type': 'ACTIVE_COMPARATOR', 'description': 'FOLFOX 6 cycles or CAPOX 4 cycles\n\n* FOLFOX regimen: 6 cycles every 2 weeks or\n* CAPOX regimen: 4 cycles every 3 weeks', 'interventionNames': ['Drug: FOLFOX or CAPOX adjuvant chemotherapy']}] | Interventions:[{'type': 'DRUG', 'name': 'mFOLFIRINOX-FOLFIRI intensified chemotherapy', 'description': '(1) Modified FOLFIRINOX (mFOLFIRINOX) regimen: 6 cycles every 2 weeks\n\n* Oxaliplatin 85mg/m2 IV infusion over 120 min D1\n* Leucovorin 400mg/m2 IV (concurrently with oxaliplatin)\n* Irinotecan 150mg/m2 IV infusion over 60-90 min D1\n* 5-fluorouracil 2,400mg/m2 IV infusion continuously over 46-48h D1-2', 'armGroupLabels': ['mFOLFIRINOX intensified chemotherapy']}, {'type': 'DRUG', 'name': 'FOLFOX or CAPOX adjuvant chemotherapy', 'description': '1. FOLFOX regimen: 6 cycles every 2 weeks\n\n * Oxaliplatin 85mg/m2 IV infusion over 120 min D1\n * Leucovorin 400mg/m2 IV infusion over 120 min (concurrently with oxaliplatin)\n * 5-fluorouracil 400mg/m2 IV bolus D1\n * 5-fluorouracil 2,400mg/m2 IV infusion continuously over 46-48h D1-2 or\n2. CAPOX regimen: 4 cycles every 3 weeks\n\n * Oxaliplatin 130mg/m2 IV infusion over 120 min D1\n * Capecitabine 1,000mg/m2 PO bid D1-14', 'armGroupLabels': ['FOLFOX or CAPOX adjuvant chemotherapy']}] | PrimaryOutcomes: [{'measure': '3-year disease-free survival rate', 'description': 'The rate refers to cases that see first tumor metastasis or recurrence or death of any cause from randomization', 'timeFrame': 'Through completion of follow-up (estimated to be 36 months)'}] | SecondaryOutcomes: [{'measure': 'Circulating tumor DNA (ctDNA) clearance rate', 'description': 'The proportion of patients with circulating tumor DNA clearance after 36months study treatment.', 'timeFrame': 'The data of ctDNA clearance rate will be collected at 10 time points'}, {'measure': '5-year overall survival rate (5y-OS rate)', 'description': 'Overall survival is defined as the time from beginning of study treatment until death due to any cause.', 'timeFrame': 'Through completion of follow-up (estimated to be 60 months)'}, {'measure': 'Treatment-Related Adverse Events', 'description': 'The number of patients with adverse events and the severity according to CTCAE v5.0.', 'timeFrame': 'Through completion of follow-up (estimated to be 36 months)'}, {'measure': 'EORTC QLQ-C30 scale', 'description': 'Using the EORTC QLQ-C30 scale (European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30) to evaluate the quality of life of patients.', 'timeFrame': 'Through completion of follow-up (estimated to be 36 months)'}] |
Title: An Open-Label, Pharmacokinetic Study of the Safety and Tolerability of Pazopanib in Combination With FOLFOX 6 or CapeOx in Subjects With Colorectal Cancer | Condition: Neoplasms, Colorectal | Keywords: pharmacokinetics, colorectal cancer, pazopanib, capecitabine, CapeOx, 5-fluorouracil, oxaliplatin, combination therapy, FOLFOX 6 | Summary: | Description: N/A | ArmGroups: [{'label': 'FOLFOX 6 + Pazopanib', 'type': 'EXPERIMENTAL', 'description': 'Subjects will receive escalating doses of Pazopanib in combination with FOLFOX 6.', 'interventionNames': ['Drug: Pazopanib', 'Drug: FOLFOX 6']}, {'label': 'CapeOx + Pazopanib', 'type': 'EXPERIMENTAL', 'description': 'Subjects will receive escalating doses of Pazopanib in combination with CapeOx. CapeOx treatment consisted of IV oxaliplatin (130 mg/m\\^2) on Day 1 plus oral capecitabine (1000 mg/m\\^2) twice daily on Days 2 through 14 of every 21-day cycle. Reduced CapeOx treatment was administered according to the same schedule as the CapeOx treatment, but the dose of capecitabine was reduced to 850 mg/m\\^2 twice daily.', 'interventionNames': ['Drug: Pazopanib', 'Drug: CapeOx']}] | Interventions:[{'type': 'DRUG', 'name': 'Pazopanib', 'description': 'Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases', 'armGroupLabels': ['CapeOx + Pazopanib', 'FOLFOX 6 + Pazopanib']}, {'type': 'DRUG', 'name': 'FOLFOX 6', 'description': 'FOLFOX 6 treatment consists of intravenous (IV) oxaliplatin (100 milligram per meter\\^2\\[mg/m\\^2\\]), and folinic acid (400 mg/m\\^2), IV 5-fluorouracil bolus (400 mg/m\\^2) followed by IV 5-fluorouracil (2400 to 3000 mg/m\\^2) infusion over 48 hours on Day 1 of every 14-day cycle.', 'armGroupLabels': ['FOLFOX 6 + Pazopanib']}, {'type': 'DRUG', 'name': 'CapeOx', 'description': 'CapeOx treatment consists of IV oxaliplatin (130 mg/m\\^2) on Day 1 plus oral capecitabine (1000 mg/m\\^2) twice daily on Days 2 through 14 of every 21-day cycle. Reduced CapeOx treatment will be administered according to the same schedule as the CapeOx treatment, but the dose of capecitabine will be reduced to 850 mg/m\\^2 twice daily.', 'armGroupLabels': ['CapeOx + Pazopanib']}] | PrimaryOutcomes: [{'measure': 'Plasma AUC(0-24) of pazopanib on Day 1, 14 and 21 Plasma AUC(0-46) of 5-FU and AUC(0-8) of platinum on Day 1 Plasma AUC(0-24) of capecitabine, 5-FU, and platinum on Day 1', 'timeFrame': 'on Day 1, 14 and 21'}] | SecondaryOutcomes: [{'measure': 'Pharmacokinetic endpoints (AUC, C24, Cmax, tmax, and half-life)collected predose and 1, 2, 3, 4, 5, 6, 8, and 24 hours on Day 1. Assessment of disease by imaging', 'timeFrame': 'collected predose and 1, 2, 3, 4, 5, 6, 8, and 24 hours on Day 1.'}] |
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