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ACTIVE NOT RECRUITING
NCT02571725
PHASE1/PHASE2

PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer

Sponsor: New Mexico Cancer Research Alliance

View on ClinicalTrials.gov

Summary

Of the approximately 21,000 cases of ovarian cancer diagnosed annually in the U.S, ten percent are attributed to hereditary syndromes, most commonly the result of mutations in the breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Mutation in these genes results in the inability to repair double-stranded breaks in DNA. Treating these tumors with poly(adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitors results in the specific killing of BRCA negative cells by blocking a second DNA-repair mechanism. Treatment of ovarian cancer patients with PARP inhibitors has resulted in improved progression free survival (PFS), but not overall survival (OS). It's not completely understood why this is the case, but some preclinical studies using ovarian cancer models in mice have suggested that combining PARP inhibitors with immune system modulators like T cell checkpoint inhibitors improves long-term survival. Therefore, the purpose of this study is to evaluate the safety and efficacy of a combination of a PARP inhibitor (Olaparib) with a T cell checkpoint inhibitor (the anti-CTLA-4 antibody Tremelimumab) in women with recurrent BRCA mutation-associated ovarian cancer.

Official title: A Phase 1-2 Study of the Combination of Olaparib and Tremelimumab, in BRCA1 and BRCA2 Mutation Carriers With Recurrent Ovarian Cancer

Key Details

Gender

FEMALE

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

50

Start Date

2016-02-23

Completion Date

2027-07-15

Last Updated

2025-05-23

Healthy Volunteers

No

Interventions

DRUG

Olaparib

Olaparib starts concomitantly with the first dose of Tremelimumab

DRUG

Tremelimumab

3 to 6 patients will be treated at 10 mg/kg depending on RLT observed in the first 3 patients. If 0 out of 3 or 1 out of 6 patients experienced a RLT at 10 mg/kg, then this dose will be considered at the recommended phase 2 dose (RP2D). If 2 out of 6 patients experience RLT at this dose within 56 days, then dose reductions as detailed in the Arm description will be carried out.

Locations (5)

Moffitt Cancer Center

Tampa, Florida, United States

Southwest Gynecologic Oncology Associates

Albuquerque, New Mexico, United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

The Ohio State University

Columbus, Ohio, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States