Intensification Treatment of Ovarian Cancer by PIPAC

Advanced epithelial ovarian cancer is frequently accompanied by peritoneal carcinomatosis, which is a major determinant of treatment failure and poor long-term prognosis. Although systemic platinum-taxane chemotherapy and cytoreductive surgery remain the foundation of first-line management, outcomes are substantially worse when intraperitoneal tumor burden is high and complete cytoreduction is difficult to achieve. In this setting, additional locoregional treatment strategies may help improve intraperitoneal disease control while preserving the feasibility of multimodal therapy. The present study evaluates pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an investigational component of combined first-line treatment for advanced ovarian cancer with peritoneal dissemination.

PIPAC delivers intraperitoneal chemotherapy as a pressurized aerosol during laparoscopy and is intended to enhance spatial distribution and tissue penetration of the drug while limiting systemic exposure. In this protocol, cisplatin-based PIPAC is integrated into the treatment pathway at predefined operative stages together with standard TC systemic chemotherapy and interval cytoreductive surgery. The study is designed as a prospective, randomized, open-label, controlled phase II trial comparing a strategy of repeated PIPAC incorporated across the course of induction and surgical treatment with a comparison strategy in which PIPAC is delivered only once during interval cytoreductive surgery. The protocol also includes further protocol-directed treatment for patients in whom complete cytoreduction is not achieved.

At the diagnostic operative stage, disease extent is documented using intra-abdominal assessment including ascites evaluation, mapping of visceral and parietal peritoneal involvement, and calculation of the Peritoneal Cancer Index. Peritoneal, ovarian, and omental tissue samples are obtained for histologic verification and subsequent treatment-response assessment. PIPAC is administered laparoscopically under general anesthesia using cisplatin diluted in normal saline, delivered into a carbon dioxide capnoperitoneum under controlled pressure and flow conditions with a fixed exposure time. Interval cytoreductive surgery is planned after induction treatment, and when indicated, an additional intraoperative PIPAC procedure is performed before abdominal-wall closure.

Throughout the study, participants undergo protocol-defined clinical, laboratory, imaging, and pathologic evaluations during treatment and follow-up. Serial reassessment of intraperitoneal disease, biopsy-based morphologic evaluation, tumor-marker monitoring, and adverse-event documentation are used to characterize treatment activity and tolerability over time. Follow-up continues at regular intervals after completion of therapy and includes oncologic surveillance and quality-of-life assessment. Safety oversight includes detailed documentation of adverse events and specific operating-room precautions intended to minimize occupational exposure during aerosolized intraperitoneal chemotherapy procedures. Study conduct, documentation, and confidentiality are governed by protocol-defined data-management procedures and ethical requirements, including written informed consent and ethics committee approval before study initiation and for major protocol amendments.

This trial is intended not only to evaluate the clinical contribution of repeated PIPAC in the first-line setting, but also to refine a practical treatment sequence for combining intraperitoneal aerosol chemotherapy with neoadjuvant systemic therapy, interval surgery, and postoperative management in patients with advanced ovarian cancer and peritoneal carcinomatosis.

• Overall survival [Time frame: From randomization through follow-up, assessed up to 2 years after completion of treatment]
• Progression-free survival [Time frame: From randomization through follow-up, assessed up to 2 years after completion of treatment]
• Recurrence rate [Time frame: From completion of treatment through follow-up, assessed up to 2 years Recurrence rate is named among the secondary endpoints.]
• Time to progression [Time frame: From randomization through follow-up, assessed up to 2 years after completion of treatment]
• Ascites response [Time frame: During treatment through follow-up, assessed up to 2 years after completion of treatment The protocol identifies rate of ascites accumulation as a secondary endpoint and also requires ascites-volume assessment at each operative stage.]
• Tumor marker response [Time frame: During treatment and follow-up, assessed up to 2 years after completion of treatment The protocol specifies the proportion of patients with at least 50% reduction in tumor-marker levels as a secondary endpoint.]
• Frequency and severity of adverse events [Time frame: From informed consent through follow-up, assessed up to 2 years after completion of treatment]
• Intestinal paresis [Time frame: During treatment, assessed through completion of treatment Intestinal paresis is specifically listed among the secondary endpoints (assessed up to 6 months)]
• Laboratory abnormalities [Time frame: During treatment and follow-up, assessed up to 2 years after completion of treatment Laboratory abnormalities are included in the secondary endpoint list, and laboratory testing is performed repeatedly during treatment and follow-up.]
• Wound-healing time [Time frame: From the date of surgery to complete wound healing, assessed up to 30 days after each study-related surgical procedure]