Rationale and study design of the kov-hipec-02 trial: a randomized, multicenter, open-label phase iii trial of hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer

Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery has emerged to achieve a higher concentration of chemotherapeutic agents and treat micro-metastases on peritoneal surfaces. At advanced staged ovarian cancer treated with neoadjuvant chemotherapy, HIPEC during interval cytoreductive surgery with cisplatin 75-100mg/m2 increases progression-free survival and overall survival (OV-HIPEC-01 and KOV-HIPEC-01). In chemotherapy-naïve ovarian cancer patients, survival benefit is not identified with HIPEC (KOV-HIPEC-01). In ovarian cancer, HIPEC is thought to overcome chemotherapy resistance. This trial (KOV-HIPEC-02) is a multicenter, open-label, 1:1 randomized, phase III trial that will enroll 140 patients in platinum-resistant recurrent epithelial ovarian cancer. The trial is registered on ClinicalTrials.gov (NCT05316181). Institutional review board approval was obtained. The experimental arm will receive cytoreductive surgery and HIPEC followed by standard chemotherapy, and the control arm will receive standard chemotherapy without HIPEC until disease progression. If patients are assigned to the HIPEC group, the HIPEC procedure is carried out using the open or closed technique with infusing 41.5-42.0°C doxorubicin 35mg/m2 and mitomycin 15mg/m2 for 90 minutes. The primary objective of the trial is to evaluate progression-free survival (PFS) between the HIPEC group and the control group. Secondary objectives are overall survival (OS), cancer-specific survival, safety and the quality of life according to whether HIPEC was performed during surgery in patients with platinum-resistant recurrent ovarian cancer. The first patient was enrolled April 2020. Assuming that the enrollment period is 3 years, and the follow-up period is 2 years, the total number of events required is 121. Based on the log-rank test, the total number of subjects required to prove HR 0.6 with a two-sided alpha 0.05 and 80% power is 126. 140 patients are finally studied considering 10% drop-out. Ovarian Cancer, HIPEC, Intraperitoneal Chemotherapy