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PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer
Sponsor: New Mexico Cancer Research Alliance
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
Olaparib
Olaparib starts concomitantly with the first dose of Tremelimumab
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