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

Part of paid clinical trials in Tampa, Florida.

Sponsor
New Mexico Cancer Research Alliance
Study ID
NCT02571725
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

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

Interventions

  • Olaparib — DRUG
    Olaparib starts concomitantly with the first dose of Tremelimumab
  • Tremelimumab — DRUG
    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.

Study Details

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.

Key Dates

Start date
Feb 23, 2016
Status verified
May 2025
Primary completion
Dec 2, 2020
Completion
Jul 15, 2027

Study Design

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

Arms

  • Experimental: Olaparib and Tremelimumab
    Each cycle is 28 days: Olaparib at 300 mg, orally, twice daily + Tremelimumab at 10 mg/kg, intravenously, every 4 weeks for the first 6 doses, then every 12 weeks until disease progression or unacceptable toxicity. * If 1 of the first 3 patients experiences a regimen-limiting toxicity (RLT), 3 more patients will be treated with 10 mg/kg Tremelimumab in Phase 1. If 2 or more of 6 patients experience RLT, then 6 mg/kg Tremelimumab will be tested * If at 6 mg/kg, 1 or more of 3 patients experience RLT, 3 patients will be treated at 3 mg/kg Tremelimumab * If at 3 mg/kg, 1 or more patients experience RLT, the study will be discontinued for safety purposes In Phase 2, patients will receive doses of Olaparib and Tremelimumab determined in the Phase 1 portion as described above, based on tolerability.

Primary Outcome Measure

Phase 1: Recommended Phase 2 Dose (RP2D) [ Time Frame: Within 56 days of first treatment (up to 2 years) ]

Locations (5)

FacilityCityStateZIPSite coordinators
Moffitt Cancer CenterTampaFlorida33612-
Southwest Gynecologic Oncology AssociatesAlbuquerqueNew Mexico87106-
University of New Mexico Comprehensive Cancer CenterAlbuquerqueNew Mexico87131-
The Ohio State UniversityColumbusOhio43210-
University of Virginia Cancer CenterCharlottesvilleVirginia22903-

Find similar trials in Tampa, FL

By condition
Ovarian cancer
By specialty
OncologyGynecologic oncologyWomen's health
By research site
Moffitt Cancer Center· Tampa, FLSouthwest Gynecologic Oncology Associates· Albuquerque, NMUniversity of New Mexico Comprehensive Cancer Center· Albuquerque, NMThe Ohio State University· Columbus, OHUniversity of Virginia Cancer Center· Charlottesville, VA

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