Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
NCT Number: NCT06580314
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Fallopian Tube Endometrioid Adenocarcinoma|Fallopian Tube High Grade Serous Adenocarcinoma|FIGO Stage III Ovarian Cancer 2014|FIGO Stage IV Ovarian Cancer 2014|Ovarian Carcinoma|Primary Peritoneal Endometrioid Adenocarcinoma|Primary Peritoneal High Grade Serous Adenocarcinoma|Ovarian High Grade Serous Adenocarcinoma
Interventions: DRUG: Olaparib|BIOLOGICAL: Bevacizumab|PROCEDURE: Biospecimen Collection|PROCEDURE: Computed Tomography|PROCEDURE: Magnetic Resonance Imaging
Sponsor: NRG Oncology
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 880
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2025-01-16
Completion Date: 2035-12-31

Summary:
This phase III trial compares the effect of olaparib for one year versus two years, with or without bevacizumab, for the treatment of BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer. Olaparib is a polyadenosine 5\&#39;-diphosphoribose polymerase (PARP) enzyme inhibitor and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving olaparib for one year with or without bevacizumab may be effective in treating patients with BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer, when compared to two years of olaparib.

Primary Outcome Measures: Progression free survival (PFS), PFS will be tested using a one-sided, alpha = 0.05 level logrank test. Treatment hazard ratios and their 95% confidence intervals will be estimated using a Cox proportional hazards model specified with a main effect for the randomized treatment assignment and stratified using the stratification factors applied at randomization., From completion of 1 year of maintenance therapy to progressive disease or death up to 5 years
Secondary Outcome Measures: PFS2, PFS2 may be identified by objective radiological progression using Response Evaluation Criteria in Solid Tumors version (v)1.1., symptomatic deterioration or death. PFS2 will be summarized using treatment hazard ratio estimates (95% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. PFS2 distributions will be summarized using methods developed by Kaplan-Meier., From randomization to objective tumor progression on next-line treatment or death up to 5 years|Incidence of adverse events (AEs), Safety and tolerability will be graded using Common Terminology Criteria for Adverse Events v 5.0. AEs will be summarized by system organ class and preferred term according to the maximum grade observed for each patient., Up to 30 days after last dose of study treatment|Overall survival (OS), OS will be summarized using treatment hazard ratio estimates (95% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. OS distributions will be summarized using methods developed by Kaplan-Meier., From randomization to death up to 5 years
Other Outcome Measures: Effect of bevacizumab on PFS, The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). PFS outcome distributions will further be described using methods developed by Kaplan-Meier., Up to 5 years|Effect of bevacizumab on OS, The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). OS outcome distributions will further be described using methods developed by Kaplan-Meier., Up to 5 years|Effect of bevacizumab on PFS2, The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). PFS2 outcome distributions will further be described using methods developed by Kaplan-Meier., Up to 5 years