Sunnybrook Health Sciences Centre
The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy. The trial is designed as an open- label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II. There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trial.The rationale for this study is that for a subset of patients, olaparib, will increase tumor cell survival dependence on inhibition of cell death by Bcl 2/Bcl- XL. Thus, navitoclax will augment apoptosis induced by PARP inhibition with olaparib.
High Grade Serous Carcinoma
Triple Negative Breast Cancer
Ovarian Cancer
Olaparib tablet
Navitoclax
Phase 1
In this trial, olaparib will be delivered alone for 14 days with the hypothesis that priming of the apoptotic machinery will be required prior to introduction of the senolytic agent (navitoclax). To date navitoclax and olaparib have not been combined in the clinic. The Phase I study will therefore be conducted to define the recommended Phase II dose (RP2D). A plan for a future Phase II study will depend on the results obtained during this Phase I trial. Based on the potential for overlapping toxicity (particularly hematologic toxicity) an interrupted dosing schedule will be used for the navitoclax. Based on preclinical studies it is believed that intermittent delivery of the senolytic agent is in line with the proposed mechanism of action. Subsequently the dose of navitoclax will be escalated with a fixed dose of olaparib in 28-day cycles.
Study Type : | Interventional |
Estimated Enrollment : | 36 participants |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Trial of the Combination of Olaparib and Navitoclax in Women With High Grade Serous Epithelial Ovarian Cancer and Triple Negative Breast Cancer |
Actual Study Start Date : | November 9, 2022 |
Estimated Primary Completion Date : | April 28, 2024 |
Estimated Study Completion Date : | April 28, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Single Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily (bid). Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated. Navitoclax will be administered daily. The initial dose of olaparib 200 mg has been selected after considering the single agent Phase I/II dose based and on ongoing combination studies on expected toxicity and evidence for reduced PARP inhibition |
Drug: Olaparib tablet Drug: Navitoclax |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Recruiting
Sunnybrook Research Institute/Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z5
Recruiting
CHUM
Montreal, Quebec, Canada, H2X 0A9