Combined Hyperthermic Intraperitoneal Chemotherapy and Normothermic Intraperitoneal Chemotherapy Long-Term After Interval Cytoreduction in Ovarian Cancer: A Phase I Clinical Trial (BICOV1)

Abstract

Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management.