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Title:
J1819 - Combination ATR and PARP Inhibitor (CAPRI) trial with AZD6738 and olaparib in recurrent ovarian cancer
Protocol Number:
J1819
Phase:
Phase II
Physician:
Stephanie Wethington
Sites:
Johns Hopkins Kimmel Cancer Center in Baltimore
Purpose:
To determine the safety and tolerability of combination AZD6738 and olaparib in recurrent ovarian cancer patients using Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Eligibility:
1. Patients equal to 18 years of age2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.3. Patients must have high grade serous ovarian, primary peritoneal, and/or fallopian tube cancer histologically or cytologically confirmed at the University of Pennsylvania or JHH that is recurrent and for which standard curative measures do not exist or are no longer effective.4. All patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies. Cohorts A & B: 75% will require all biopsies (Pre-Tumor, On-Treatment, PD). If safe, 25% will require a biopsy only at PD. Cohort C: 100% will require all biopsies (Pre-Tumor, On-Treatment, PD).5. All patients must have a measurable disease by RECIST v1.1.
Treatment:
This is an open label, non-randomized two-stage phase II study to examine activity of the combination of AZD6738 and olaparib in 3 cohorts of approximately 86 patients:Cohort A: recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), n equal to 37 with interim analysis after 17 patientsCohort B: recurrent platinum-resistant ovarian cancer (progression less than 6 months of the last receipt), n equal to 37 with an interim analysis after 12 patientsCohort C: PARP inhibitor (PARPi) resistant (patients who have progressed on PARPi monotherapy), Patients must be platinum sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. n equal to 12The cohorts will be open concurrently and treatment assignment will be based on platinum- sensitivity.All patients will receive the combination of AZD6738 and olaparib. Patients will receive olaparib 300 mg BD in combination with AZD6738 at 160 mg OD. Patients who agree to consent to the PARP inhibitor tracer study (maximum of 10 patients per cohort; 30 patients total) will have a 7 day lead in of olaparib 300 mg BD daily prior to starting the combination of AZD6738 160 mg OD and olaparib 300 mg BD. If necessary, this lead-in period can be shortened to 6 or 5 days, however 7 days is ideal. The AZD6738 will be dosed on days 1-7. The olaparib will be dosed on days 1-28. Each cycle will be 28 days and begins upon administration of medication on Day 1 of each cycle. Prior to the initiation of this study, it is expected that there will be less than 100 subjects treated with the combination in a phase I trial and most of these will be subjects with gastric cancer. Thus, there will not be extensive prior experience with the combination in ovarian cancer and the safety profile of the combination has not been fully determined. As a result, prior to expanding the platinum sensitive (Cohort A) and platinum resistant (Cohort B) cohorts to the maximum of 37 patients each, the safety data will be reviewed alongside the efficacy response data in the interim analysis to ensure the risk benefit ratio supports expansion.
Population:
Adult
Last Update
08/07/2020 05:02 AM