Status:
ACTIVE_NOT_RECRUITING
Combination of Olaparib and Navitoclax in Women with HGSC and TNBC
Lead Sponsor:
Sunnybrook Health Sciences Centre
Collaborating Sponsors:
Exactis Innovation
Centre hospitalier de l'Université de Montréal (CHUM)
Conditions:
High Grade Serous Carcinoma
Triple Negative Breast Cancer
Eligibility:
FEMALE
18+ years
Phase:
PHASE1
Brief Summary
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 m...
Detailed Description
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 d...
Eligibility Criteria
Inclusion
- Inclusion
- Histologically confirmed:
- Recurrent metastatic HGSC of ovarian, peritoneal or fallopian tube origin with radiological progression greater than 6 months from last platinum based therapy.
- Metastatic TNBC: tumors that are known to have deleterious somatic or germline mutations in BRCA1, BRCA2, or PALB2.
- Age ≥ 18 years of age.
- ECOG Performance Status of 0, 1 or 2 within 7 days prior to registration (Appendix 4).
- No more than two (2) prior lines of treatment for TNBC.
- No limit on the number of prior lines for HGSC.
- Prior maintenance or treatment with PARP inhibitor is allowed provided progression did not occur on or within 6 months of discontinuing the drug. Patients must be considered able to tolerate olaparib as per dosing regimen in this study.
- Patients must be able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption.
- Patients must be able and willing to undergo study related procedures (biopsies pre and on treatment) and to provide archival tissue, if available.
- Patients must have a life expectancy ≥16 weeks.
- Patients must have adequate organ and marrow function measured within 28 days prior to administration of study drug
- Patients must have measurable disease as defined by RECIST 1.1. Progressive irradiated lesions considered but would require an additional out of field measurable lesion.
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
- Exclusion
- Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within 30 days prior to first dose of investigational products (IPs).
- Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed within 14 days of the olaparib lead-in period: Warfarin, clopidogrel (plavix), ibuprofen, tirofiban (aggrastat), and other anticoagulants drugs including low molecular weight heparin, or herbal supplements that affect platelet function are excluded. Caution should be exercised when dosing Navitoclax concurrently with CYP2C8 and CYP2C9 substrates.
- Due to the known effects of navitoclax on platelet counts, patients with active bleeding or thrombocytopenia-associated bleeding within 1 year, active peptic ulcer disease or potentially hemorrhagic esophagitis or gastritis, a requirement for concurrent therapeutic anticoagulants, or a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, or refractoriness to platelet transfusions.
Exclusion
Key Trial Info
Start Date :
November 9 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 28 2025
Estimated Enrollment :
36 Patients enrolled
Trial Details
Trial ID
NCT05358639
Start Date
November 9 2022
End Date
April 28 2025
Last Update
November 18 2024
Active Locations (3)
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1
Sunnybrook Research Institute/Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
2
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z5
3
CHUM
Montreal, Quebec, Canada, H2X 0A9