Comparison of Body Surface Area-Based Versus Concentration-Based Dosing of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy for Advanced Ovarian Cancer

The primary objective of this study is to evaluate **body surface area (BSA)-based** versus concentration-based dosing of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced-stage ovarian cancer. This comparison is clinically relevant as it aims to optimize dosing strategies to improve treatment efficacy and minimize toxicity in women with FIGO stage III high-grade serous ovarian cancer, peritoneal cancer, or fallopian tube carcinoma.

Secondary objectives include:

• Comparing pharmacokinetic parameters between treatment arms to understand the drug's absorption, distribution, metabolism, and excretion.
• Determining the toxicity for each treatment arm to assess safety and tolerability.
• Comparing recurrence-free and overall survival between treatment arms to evaluate long-term outcomes and effectiveness.

The clinical trial involves a study population consisting exclusively of **female** participants diagnosed with FIGO stage III high-grade serous **ovarian cancer**, peritoneal cancer, or fallopian tube carcinoma. The age range of the participants is 18 years and older. The trial does not include a vulnerable population. Participants were selected based on specific inclusion criteria, such as adequate renal, bone marrow, and hepatic function, and a WHO performance status of 0-2, indicating they are fit for major surgery. All participants have undergone optimal or complete interval cytoreductive surgery and have peritoneal disease present at the start of this surgery. The trial does not provide information on the total number of participants, as the sponsor has not disclosed this data. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate **body surface area (BSA)**-based versus concentration-based dosing of **cisplatin** for hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. This is a Phase II, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on September 1, 2022, and conclude by March 1, 2025. Participants will be randomly assigned to receive either BSA-based or concentration-based dosing of cisplatin, administered as a solution for infusion via intraperitoneal use. The primary endpoint is the measurement of intratumoral platinum concentration at the end of a 90-minute perfusion. Secondary endpoints include toxicity evaluation, platinum concentration in normal and tumor tissues at various time points, and recurrence-free and overall survival.

The trial will involve several study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as adequate renal and hepatic function, bone marrow function, and fitness for major surgery. Participants must provide signed informed consent and meet specific inclusion criteria, including a diagnosis of FIGO stage III high-grade serous ovarian cancer, peritoneal cancer, or fallopian tube carcinoma. Follow-up visits will be scheduled to monitor treatment response and adverse events, with the end-of-study visit marking the completion of the trial. The expected length of participant involvement is approximately 30 months, depending on individual treatment response and progression.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it in their best interest. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **Cisplatin**, an antineoplastic agent, as the experimental medication. The product used is "Cisplatine Accord 1 mg/ml concentraat voor oplossing voor infusie," which is a **solution for infusion**. The active substance, **cisplatin**, is of chemical origin. The pharmaceutical form is a concentrate for solution for infusion, and it is administered via the **intraperitoneal route**. The maximum daily dose is 220 mg, with a total maximum dose of 220 mg over the treatment period. The treatment period is limited to one day. The medication is not a pediatric formulation and is not classified as an orphan drug. The product is manufactured by Accord Healthcare B.V. and is authorized for use in the Netherlands.

In this study, the experimental treatment is compared against a standard-of-care therapy, which involves body surface area-based versus concentration-based dosing of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. The trial aims to evaluate the efficacy of these dosing strategies in patients with advanced-stage ovarian cancer. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. No additional non-experimental treatments, such as placebo or comparator treatments, are specified in the trial documentation.

The clinical trial aims to assess the efficacy of **cisplatin** in the context of hyperthermic intraperitoneal chemotherapy (HIPEC) for women with advanced ovarian cancer. The primary endpoint for evaluating efficacy is the measurement of intratumoral platinum (Pt) concentration at the end of a 90-minute perfusion, quantified in ng/mg of wet tissue. Secondary endpoints include the evaluation of toxicity using CTCAE 5.0, Pt concentration in normal tissue, and Pt concentration in tumor tissue after 30 and 60 minutes of perfusion. Additionally, the concentration versus time curve and area under the curve (AUC) of intra-peritoneal Pt during perfusion will be analyzed, along with Cmax, tmax, terminal half-life in perfusate, and clearance from perfusate at the end of perfusion. Recurrence-free survival (RFS) and overall survival (OS) will also be assessed as part of the secondary endpoints.