This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.
This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 1 prior line of platinum-based chemotherapy. The study will assess the effectiveness of olaparib tablets as measured by the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice® HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA analysis and HRD status. Four cohorts will be identified based upon the genetic testing described above: * Cohort 1: gBRCAm, * Cohort 2: sBRCAm and germline BRCA wild type, * Cohort 3: myChoice® HRD positive (genomic instability positive) and BRCA wild type (BRCAwt) (no BRCA mutation), * Cohort 4: myChoice® HRD negative (genomic instability negative) and BRCAwt (no BRCA mutation).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
272
300 mg olaparib tablets taken orally twice daily
Objective Response Rate, Defined as the Percentage of Subjects With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using ORR according to RECIST v1.1 criteria (Investigator determined)
Time frame: From first dose up until progression, or last evaluable assessment in the absence of progression (up to 36 months)
Duration of Response, for Those Subjects With a Confirmed Response of CR or PR
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using duration of response
Time frame: From the date of the measurement criteria for CR or PR are first met until the date of documented progression or death in the absence of disease progression (up to 36 months)
CA-125 Response Rate, Defined as the Percentage of Subjects With a CA-125 Response According to GCIG Criteria Divided by the Number of Subjects Evaluable for CA-125 Response
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using CA-125 response rate
Time frame: From baseline to Day 1 of each cycle and end of study treatment visit (up to 36 months)
Disease Control Rate Defined as the Percentage of Subjects Who Have a Best Overall Response of CR or PR or SD at Greater Than or Equal to 8 Weeks Divided by the Number of Subjects in the Efficacy Analysis Set, Prior to Any PD Event
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using disease control rate (DCR). DCR is defined as the percentage of subjects with a best overall response of CR or PR (at any time up to and including the defined analysis cut-off point) or who have demonstrated stable disease (SD) for at least 8 weeks from first dose, divided by the number of subjects in the efficacy analysis set.
Time frame: From first dose up until progression, or last evaluable assessment in the absence of progression
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Research Site
Anchorage, Alaska, United States
Research Site
La Jolla, California, United States
Research Site
Los Angeles, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Hartford, Connecticut, United States
Research Site
New Haven, Connecticut, United States
Research Site
Newark, Delaware, United States
Research Site
South Miami, Florida, United States
Research Site
Skokie, Illinois, United States
Research Site
Shreveport, Louisiana, United States
...and 37 more locations
Progression Free Survival
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using progression free survival
Time frame: From first dose to earlier date of assessment of objective progression or death by any cause in the absence of progression (up to 36 months)
Time to Any Progression
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using time to any progression
Time frame: From first dose to earlier date of CA-125 progression or RECIST v1.1 progression, or death by any cause in absence of progression (up to 36 months)
Overall Survival
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using overall survival
Time frame: From date of first dose to date of death from any cause (up to 48 months)
HRD Status as Per HRRm Gene Panel Assessment Will be Correlated With Clinical Outcome (ORR) for Subjects Enrolled in the 2 Cohorts With BRCAwt (Cohorts 3 and 4)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using HRRm gene panel status related to clinical outcome
Time frame: At baseline