A Phase III Trial of One vs. Two Years of Maintenance Olaparib, With or Without Bevacizumab, in Patients With BRCA1/2 Mutated or Homologous Recombination Deficient (HRD+) Ovarian Cancer Following Response to First Line Platinum Based Chemotherapy
Primary Objective To determine investigator assessed progression-free survival using RECIST v1.1 (non-inferiority) for one vs. two years of maintenance olaparib. This analysis is supported by a modified ITT population limited to patients on protocol at least 360 days after randomization. The time at risk for this population starts 360 days after randomization (Section 15.3). This analysis is denoted PFS360. Secondary Objectives To evaluate overall survival (OS360) in the modified ITT population, with time at risk for progression/death starting 360 days after randomization To evaluate PFS, PFS2 and OS in the ITT population To evaluate PFS, PFS2, and OS in the as-treated population. To evaluate toxicity, including rates of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and other secondary malignancies, in the safety population. Exploratory Objectives To evaluate the moderating effect of physician-choice bevacizumab (as stratified Section 15.2) on randomized treatment effect estimates. Endpoints for these analyses include PFS, PFS2, and OS, as supported by the ITT population. Translational Objectives Testing of banked biospecimens will not occur until an amendment to this protocol (or a separate correlative science proposal) is reviewed and approved in accordance with National Clinical Trials Network (NCTN) policies. 1. To assess BRCA reversion mutations in ctDNA as a predictor of poor response in the BRCA mutated (BRCAm) population. 2. To correlate a combined assay assessing quantitative BRCA1 and RAD51C promoter methylation and pathogenic variants in core homologous recombination repair (HRR) genes with clinical HRD testing and outcomes in the BRCA wildtype (BRCAwt) population.