Testing Olaparib for One or Two Years, with or without Bevacizumab, to Treat Ovarian Cancer

Active:	Yes
Cancer Type:	Ovarian Cancer	NCT ID:	NCT06580314
Trial Phases:	Phase III	Protocol IDs:	NRG-GY036 (primary) NRG-GY036 NCI-2024-04335
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	NRG Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT06580314

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'-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.

Objectives

PRIMARY OBJECTIVE:
I. To determine investigator assessed progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (non-inferiority) for one versus (vs.) two years of maintenance olaparib.

SECONDARY OBJECTIVES:
I. To evaluate overall survival (OS360) in the modified intent to treat (ITT) population, with time at risk for progression/death starting 360 days after randomization.
II. To evaluate progression-free survival (PFS), PFS2 and overall survival (OS) in the ITT population.
III. To evaluate PFS, PFS2, and OS in the as-treated population.
IV. To evaluate toxicity, including rates of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and other secondary malignancies, in the safety population.

EXPLORATORY OBJECTIVE:
I. To evaluate the moderating effect of physician-choice bevacizumab (as stratified) on randomized treatment effect estimates.

TRANSLATIONAL OBJECTIVES:
I. To assess BRCA reversion mutations in circulating tumor deoxyribonucleic acid (ctDNA) as a predictor of poor response in the BRCA mutated (BRCAm) population.
II. To correlate a combined assay assessing quantitative BRCA1 and RAD51C promoter methylation and pathogenic variants in core homologous recombination repair (HRR) genes with clinical homologous recombination deficiency (HRD) testing and outcomes in the BRCA wildtype (BRCAwt) population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (REFERENCE): Patients receive olaparib orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study.

ARM II (EXPERIMENTAL): Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Treatment Sites in Georgia

University Cancer and Blood Center, LLC - Athens Medical Oncology
3320 Old Jefferson Road
Building 800
Athens, GA 30607
www.universitycancer.com

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.