Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

Abstract

Background: Poly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.

Primary objective: To determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.

Study hypothesis: Olaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.

Trial design: Phase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator's choice.

Major eligibility criteria: Eligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.

Primary endpoint: The dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.

Sample size: Approximately 200 patients will be enrolled in this study.

Estimated dates for completing accrual and presenting results: Enrollment will be completed in 2024. Results will be presented in 2026.

Trial registration: EudraCT 2021-000245-41 NCT05255471.

Keywords: BRCA1 protein; BRCA2 protein; ovarian cancer.