Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer
Phase 2
Active, not recruiting
- Conditions
- High Grade Serous Carcinoma
- Interventions
- Drug: Olaparib PillDrug: AZD6738
- Registration Number
- NCT03462342
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
Investigational agent, AZD6738 will be given in combination with Olaparib to women with recurrent ovarian cancer (platinum-sensitive or platinum-resistant).
This study will determine if using Olaparib in combination with AZD6738 is safe and tolerable and also determine the objective response rate and progression free survival of combination of AZD6738 and Olaparib in women with recurrent ovarian cancer in distinct platinum-sensitive and platinum-resistant cohorts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 86
Inclusion Criteria
Not provided
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Exclusion Criteria
Not provided
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A. Olaparib Pill + AZD6738. Olaparib Pill Cohort A: Recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), approximately 37 patients could be treated with an interim analysis after 17 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. A. Olaparib Pill + AZD6738. AZD6738 Cohort A: Recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), approximately 37 patients could be treated with an interim analysis after 17 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. B. Olaparib Pill + AZD6738. AZD6738 Cohort B: Recurrent platinum-resistant ovarian cancer (progression less than or equal to 6 months of the last receipt), approximately 37 patients could be treated with an interim analysis after 12 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. C. Olaparib Pill + AZD6738. AZD6738 Cohort C: PARP inhibitor (PARPi) resistant (subjects who have progressed on a PARPi), patients must be platinum-sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 subjects could be treated. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. D-1. Olaparib Pill + AZD6738. AZD6738 Cohort D Part I: Patients will be platinum sensitive/platinum resistant ovarian cancer. Patient may or may not have received prior PARPi and will be enrolled irrespective of their BRCA status. The number of subjects treated will depend on the number of dose levels explored with a minimum of 12 subjects up to 30 subjects. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. D-2 Olaparib Pill + AZD6738. AZD6738 Cohort D Part II: Patients with ovarian cancer who are PARP inhibitor (PARPi) resistant (patients who have progressed on a PARPi). Patients must be platinum-sensitive and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 patients will be treated. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. B. Olaparib Pill + AZD6738. Olaparib Pill Cohort B: Recurrent platinum-resistant ovarian cancer (progression less than or equal to 6 months of the last receipt), approximately 37 patients could be treated with an interim analysis after 12 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. C. Olaparib Pill + AZD6738. Olaparib Pill Cohort C: PARP inhibitor (PARPi) resistant (subjects who have progressed on a PARPi), patients must be platinum-sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 subjects could be treated. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. D-1. Olaparib Pill + AZD6738. Olaparib Pill Cohort D Part I: Patients will be platinum sensitive/platinum resistant ovarian cancer. Patient may or may not have received prior PARPi and will be enrolled irrespective of their BRCA status. The number of subjects treated will depend on the number of dose levels explored with a minimum of 12 subjects up to 30 subjects. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. D-2 Olaparib Pill + AZD6738. Olaparib Pill Cohort D Part II: Patients with ovarian cancer who are PARP inhibitor (PARPi) resistant (patients who have progressed on a PARPi). Patients must be platinum-sensitive and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 patients will be treated. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events 2 years Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 for all cohorts.
Response rate 2 years Objective response rate (CR+PR) of the combination of AZD6738 and olaparib in women with recurrent ovarian cancer in platinum-sensitive and resistant, and PARP inhibitor resistant cohorts (e.g. Cohorts A, B, C, and D).
- Secondary Outcome Measures
Name Time Method Progression free survival 2 years Clinical anti-tumor effect by standard criteria (RECIST)
Trial Locations
- Locations (3)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States