325TiP - A phase III randomized controlled trial in primary stage three and four ovarian cancer after interval cytoreductive surgery (FOCUS/KOV-HIPEC-04)

Background

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery increases progression-free and overall survival for patients with advanced-stage epithelial ovarian cancer in two randomised controlled trials (OV-HIPEC-01 and KOV-HIPEC-01). The aim of this trial is to identify the survival benefit of HIPEC in advanced ovarian cancer in the era of maintenance therapy of bevacizumab and/or PARP inhibitor.

Trial design

The KOV-HIPEC-04 is a multicenter, 1:1 randomised, phase III trial that will enroll 520 patients with primary epithelial ovarian cancer who completed neoadjuvant chemotherapy. Patients will be randomised at the time of interval cytoreductive surgery with achieving complete cytoreduction or cytoreduction with no more than 2.5mm of residual disease to receive HIPEC (experimental arm, 41.0-42.0°C cisplatin 75mg/m², 90 minutes) or not (control arm). After recovery from surgery, patients will receive postoperative platinum-based adjuvant chemotherapy followed by maintenance therapy with PARP inhibitor or bevacizumab. The primary endpoint is to evaluate overall survival (OS); secondary objectives are progression-free survival (PFS), cancer-specific survival, time to first subsequent therapy, safety, and quality of life. Assuming that the enrollment period is five years and the follow-up period is three years, the total number of events required is 263. Based on the log-rank test, the total number of subjects required to prove HR is 0.67 with a two-sided alpha of 0.05 and 90% power is 494. 520 patients are finally studied, considering 5% drop-out.

Clinical trial identification

NCT05827523; April 25, 2023.

Legal entity responsible for the study

The authors.

Funding

National Cancer Center, Republic of Korea.

Disclosure

All authors have declared no conflicts of interest.