Phase III Randomized Study of Hyperthermic Intraperitoneal Chemotherapy with Cisplatin for Recurrent Resectable Ovarian Epithelial Cancer

The primary objective of this study is to assess the improvement in **overall survival** at 12 months for patients with ovarian epithelial cancer experiencing intraperitoneal resectable relapse, comparing those treated with hyperthermic intraperitoneal chemotherapy (HIPEC) to those without HIPEC. This is clinically relevant as it aims to determine the efficacy of HIPEC in extending survival in this patient population.

Secondary objectives include:

• Evaluating **relapse-free survival**.
• Assessing **quality of life** and pain using QLQ C30 and FACT O forms, along with the Visual Analogue Scale (VAS).
• Evaluating treatment-related **toxicities**, including renal toxicities, using CTC-AE v4.0.
• Assessing **morbidity**.
• Conducting a medico-economic study to collect socio-demographic data and patient-related management costs.
• Performing a pharmacokinetic study to compare HIPEC techniques (open abdomen and closed abdomen) by analyzing platinum concentrations at peritoneal, plasma, and tissue levels.

The clinical trial involves a total of **15 participants** diagnosed with **ovarian epithelial cancer** experiencing an intraperitoneal resectable relapse. The study population includes both male and female subjects, with an age range starting from 18 years and above. Participants were selected based on specific health criteria, including adequate hematological function, absence of contraindications to general anesthesia, and a performance status of WHO less than 2. All participants must have previously undergone treatment for epithelial ovarian cancer and exhibit a resectable intraperitoneal relapse without distant metastasis. Lifestyle considerations such as the use of appropriate contraception for women of child-bearing age during and after treatment are required. The trial does not exclude vulnerable populations, and participants must have medical or public health insurance coverage. The selection process ensures that participants have no significant hepatic or renal insufficiency, and they must have completed second-line platinum-based pre-operative chemotherapy within a specified timeframe before surgery.

The clinical trial is a **randomized**, phase III study designed to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of ovarian epithelial cancer with intraperitoneal resectable relapse. The primary objective is to improve overall survival at 12 months for patients receiving HIPEC compared to those who do not. The trial employs a **double-blind** methodology to ensure unbiased results, with participants randomly assigned to either the treatment or control group. The trial is expected to conclude by April 2025, with recruitment having commenced in April 2011.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, hematological function, and previous treatment history. Following successful screening, participants will be enrolled and randomized. The study includes follow-up visits to monitor treatment effects, assess **treatment toxicity**, and evaluate **quality of life** using standardized forms such as the QLQ C30 and FACT O. The end-of-study visit will occur after the final follow-up, where overall survival and secondary endpoints, including **relapse-free survival** and **morbidity**, will be assessed.

Participant involvement is expected to last until the end of the study, with conditions for early termination including significant adverse events or withdrawal of consent. The trial will also conduct a **pharmacokinetic study** on a subset of 50 patients to analyze platinum concentrations at various levels. The study's design ensures comprehensive data collection to evaluate the potential benefits of HIPEC in improving survival outcomes for patients with ovarian cancer relapse.

The clinical trial involves the administration of **CISPLATIN**, an experimental medication used in the treatment of ovarian cancer relapse. **CISPLATIN** is provided in the form of a **SOLUTION FOR INJECTION** and is administered via **INTRAPERITONEAL USE**. The active substance in this medication is **CISPLATIN**, which is of chemical origin. The dosage is calculated based on body surface area, with a maximum daily dose of 75 mg/m². The treatment period is limited to a maximum of one day. The administration of **CISPLATIN** is intended to evaluate its efficacy in improving overall survival at 12 months for patients receiving hyperthermic intraperitoneal chemotherapy (HIPEC) compared to those not receiving HIPEC.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, although specific details are not provided in the available data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to assess the potential benefits of **CISPLATIN** in the context of HIPEC for patients experiencing a relapse of ovarian cancer.

Efficacy in the clinical trial titled "CHIPOR: Randomized phase III study evaluating hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer relapse" will be assessed using several primary and secondary endpoints. The primary endpoint is overall survival, with the main parameter being the date of death, regardless of cause. Secondary endpoints include **relapse-free survival**, which will be determined by the absence of clinical, biological, or medical imaging evidence of relapse. This includes the presence of a mass or effusion with cytological diagnosis, confirmed elevation of CA 125 markers according to RUSTIN criteria, or detection of a measurable mass using the new RECIST criteria.

Additional secondary endpoints involve the evaluation of pain and quality of life, which will be assessed using the QLQ C30 form from EORTC and the FACT O form specific for ovarian cancer. Pain will be measured using the Visual Analogue Scale (VAS), and any history of chronic pain will be considered in the analysis. Treatment toxicity, particularly renal toxicity, will be evaluated using the CTC-AE v4.0 scale. Morbidity will be assessed up to the 60th day post-surgery, considering deaths and severe complications. A medico-economic study will collect socio-demographical data and patient management costs. Furthermore, a pharmacokinetic study will be conducted on 50 patients who received HIPEC, analyzing platinum concentrations at the peritoneal, plasma, and tissue levels.