Rucaparib and Irinotecan in Cancers With Mutations in DNA Repair
- Conditions
- Solid Tumor, Unspecified, Adult
- Interventions
- Registration Number
- NCT03318445
- Lead Sponsor
- Pamela Munster
- Brief Summary
This is an open label, non-randomized, dose escalation and expansion Phase Ib trial to evaluate the safety and recommended phase II dose of the combination of irinotecan and rucaparib.
- Detailed Description
In dose escalation, patients will receive irinotecan and rucaparib. Irinotecan will be given once every 2 weeks (or 3 weeks if not tolerated) and rucaparib will be given twice daily for 7-14 days. Each cycle will be 28 days in duration unless we need to switch to the intermediate dosing regimen of every 21 days. Both rucaparib and irinotecan will be escalated.
In dose expansion, patients who have received prior PARP inhibitors will go straight to the combination arm of irinotecan and rucaparib. If patients are PARP inhibitor naïve, they can receive single agent rucaparib until progression. Once patients on single agent rucaparib progress, they can choose to go on the combination treatment arm. Patients will continue on treatment until disease progression or intolerable toxicity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rucaparib and irinotecan Irinotecan Rucaparib will be taken twice daily by mouth for 7-14 days in 21 or 28 day cycles. Irinotecan will be administered by IV for 90 minutes every 14 days, or every 21 days if not tolerated. During the dose escalation phase, the maximum tolerated dose for combining Rucaparib and irinotecan will be determined. The dose for rucaparib during dose escalation will range from 300 mg to 600 mg, depending on the progression of study. The dose for irinotecan during dose escalation may range from 40 mg/m2 to 150 mg/m2. During the dose expansion phase, patients who have received prior PARP inhibitors will be given rucaparib and irinotecan at the maximum tolerated dose levels determined during the dose escalation phase. Rucaparib only Rucaparib During the dose expansion phase, patients who have not received prior PARP inhibitor therapy will take 600 mg of rucaparib by mouth daily. Patients who progress on single-agent rucaparib will be given the option to cross-over to the combination treatment arm and receive rucaparib in combination with irinotecan at the maximum tolerated dose levels determined during dose escalation. Rucaparib and irinotecan Rucaparib Rucaparib will be taken twice daily by mouth for 7-14 days in 21 or 28 day cycles. Irinotecan will be administered by IV for 90 minutes every 14 days, or every 21 days if not tolerated. During the dose escalation phase, the maximum tolerated dose for combining Rucaparib and irinotecan will be determined. The dose for rucaparib during dose escalation will range from 300 mg to 600 mg, depending on the progression of study. The dose for irinotecan during dose escalation may range from 40 mg/m2 to 150 mg/m2. During the dose expansion phase, patients who have received prior PARP inhibitors will be given rucaparib and irinotecan at the maximum tolerated dose levels determined during the dose escalation phase.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to 24 months. ORR is defined as the proportion of patients with either confirmed complete or partial response (as per RECIST version 1.1) as best overall response over the total population.
- Secondary Outcome Measures
Name Time Method Median Response duration Up to 24 months Response duration is defined as the time from initial response to the first documented tumor progression.
Trial Locations
- Locations (1)
University of California San Francisco
🇺🇸San Francisco, California, United States