A randomized, multicenter, open-label phase III trial of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer: a rationale and study design of the KOV-HIPEC-02 trial.

Background: This study aimed to identify the survival benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery for platinum-resistant recurrent ovarian cancer.

Primary objectives: The primary objective is to evaluate the efficacy of cytoreductive surgery and HIPEC on progression-free survival in platinum-resistant recurrent ovarian cancer.

Study hypothesis: The implementation of cytoreductive surgery and HIPEC combined with doxorubicin and mitomycin C may extend progression-free survival with manageable safety in patients with platinum-resistant recurrent ovarian cancer.

Trial design: This trial (KOV-HIPEC-02) is a multicenter, open-label, 1:1 randomized, phase III trial that enrolled 140 patients with platinum-resistant recurrent ovarian cancer. The patients will receive or will not receive cytoreductive surgery and HIPEC with doxorubicin 35 mg/m² and mitomycin 15 mg/m². Enrolled patients will receive non-platinum compound systemic chemotherapy until disease progression.

Major inclusion/exclusion criteria: Patients with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer, who demonstrate resistance or refractory to platinum-based chemotherapy, are eligible for this trial. Patients exhibiting resectable intraperitoneal disease, as determined by clinical history, recent imaging findings, and laparoscopic assessment, will be enrolled. Furthermore, they must have an Eastern Cooperative Oncology Group Performance Status of 0 to 2, a life expectancy of at least 3 months, adequate organ function, and must provide informed consent to participate in the study.

Primary endpoint: Progression-free survival defined as the time from random assignment in a clinical trial to disease progression or death from any cause.

Sample size: Assuming that the enrollment period is 3 years and the follow-up period is 2 years, 140 patients will be randomized in this study design (70 patients in the HIPEC group and 70 patients in the control group).

Estimated dates for completing accrual and presenting results: The expected date of interim analysis of primary end point is early 2025, and the patient enrollment is expected to be completed in 2025.

Trial registration: The trial is registered at ClinicalTrials.gov (NCT05316181).