Rationale and study design of the KOV-HIPEC-04: A phase III randomized controlled trial in primary stage III and IV ovarian cancer after interval cytoreductive surgery (FOCUS)

초록

Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery increases progression-free and overall survival for patients with stage III ovarian cancer in two randomized controlled trials (OV-HIPEC-01 and KOV-HIPEC-01) in the era of platinum. The aim of this trial is to identify the survival benefit of HIPEC in stage III & IV ovarian cancer with maintenance therapy of bevacizumab and/or PARP inhibitor. Methods: The KOV-HIPEC-04 trial is the international, multicenter, 1:1 randomized, phase III trial that will enroll 520 patients with stage III & IV ovarian cancer who received neoadjuvant chemotherapy. Patients with residual tumor < 2.5mm after interval cytoreductive surgery will be randomized to the trial arm (HIPEC, 41.0-42.0°C cisplatin 75mg/m2, 90 minutes) or control arm. After recovery from surgery, patients will receive postoperative platinum-based adjuvant chemotherapy followed by maintenance therapy with PARP inhibitor or bevacizumab by the institutional guideline based on BRCA/HRD status. The primary endpoint is to evaluate overall survival (OS); secondary objectives are progression-free survival (PFS), cancer-specific survival, time to the first subsequent therapy, safety, and quality of life. Assuming that the enrollment period is 5 years and the follow-up period is 3 years, the total number of events required is 263. Based on the log-rank test, the total number of subjects required to prove HR 0.67 with a two-sided alpha of 0.05 and 90% power is 494. Considering 5% drop-out, 520 patients are finally enrolled. ClinicalTrials.gov (NCT05827523). Clinical trial information: NCT05827523.