Combination of Olaparib and Navitoclax in Women with HGSC and TNBC

Sponsor
Sunnybrook Health Sciences Centre
Study ID
NCT05358639
Phase
PHASE1
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaparib tablet — DRUG
    Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily. Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated.
  • Navitoclax — DRUG
    For navitoclax, a lead-in of 7 days at 150 mg PO will be used prior to dose escalation. The DLT period for dose levels above DL 3 will include the 14-day olaparib alone lead-in, the 7 days combination with navitoclax at 150 mg and the first 28 day cycle of the combination of olaparib and navitoclax cycle at the full dose level dosing (49 days).

Study Details

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.

Key Dates

Start date
Nov 9, 2022
Status verified
Nov 2024
Primary completion
Mar 30, 2025
Completion
Apr 28, 2025

Study Design

Enrollment
36 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • 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

Primary Outcome Measure

To define a dose and schedule of navitoclax (Recommended Phase II Dose, RP2D) that can be combined safely with Olaparib in women with metastatic recurrent high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) for further study [ Time Frame: 2 years ]

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