Comparison of Perioperative and Adjuvant mFOLFIRINOX Regimens in Patients with Resectable Non-Metastatic Pancreatic Cancer

The primary objective of the PREOPANC-3 study is to investigate whether **perioperative mFOLFIRINOX** improves overall survival compared to adjuvant mFOLFIRINOX in patients with **resectable pancreatic cancer**. This is clinically relevant as it aims to determine the most effective timing for administering mFOLFIRINOX, potentially enhancing survival outcomes for patients with this condition. No secondary objectives are specified for this study.

The clinical trial involves participants diagnosed with **non-metastatic resectable pancreatic cancer**. The study population includes both male and female subjects aged 18 years and older, with no specific upper age limit indicated. Participants are required to have a **WHO performance status** of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not include vulnerable populations. The selection criteria ensure that participants have a histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma, with resectable tumors as per DPCG criteria, and no evidence of metastatic disease. Participants must have adequate hematological and renal function to undergo surgery and mFOLFIRINOX chemotherapy. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy of perioperative mFOLFIRINOX compared to adjuvant mFOLFIRINOX in patients with **non-metastatic resectable pancreatic cancer**. This is a multicenter, randomized, double-blind, controlled Phase III study. The trial aims to determine whether perioperative administration of mFOLFIRINOX improves overall survival compared to its adjuvant use. The study is expected to run from July 2021 to February 2026, with the primary endpoint being overall survival by intention to treat.

Participants will be randomly assigned to receive either perioperative or adjuvant mFOLFIRINOX. The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed pancreatic ductal adenocarcinoma, age of 18 years or older, and a WHO performance status of 0 or 1. Participants must also meet specific laboratory criteria, including adequate leucocyte, platelet, and hemoglobin levels, as well as sufficient renal function.

Following the screening visit, participants will undergo a series of follow-up visits to monitor treatment response and manage any adverse effects. These visits will include assessments of tumor resectability, chemotherapy administration, and regular health evaluations. The end-of-study visit will occur after the completion of the treatment period, which is a maximum of 38 weeks, to assess the final outcomes and gather data for analysis.

Participant involvement is expected to last for the duration of the treatment period, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include the development of metastatic disease, inability to tolerate the chemotherapy regimen, or withdrawal of consent. The trial will adhere to strict ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Irinotecan Hydrochloride Trihydrate**, marketed as Irinotecan HCl-trihydraat Accord 20 mg/ml. This medication is provided as a **solution for infusion** and is administered via infusion. The dosage is calculated based on body surface area, with a maximum daily dose of 150 mg/m² and a total maximum dose of 1800 mg/m² over a treatment period of up to 38 weeks. The active substance is of chemical origin, and the product is manufactured by Accord Healthcare B.V.

**Oxaliplatin**, under the brand name Oxaliplatine Fresenius Kabi 5 mg/ml, is also used in this study. It is available as a **solution for infusion** and is administered through infusion. The dosing is similarly based on body surface area, with a maximum daily dose of 85 mg/m² and a total maximum dose of 1020 mg/m² over the same treatment period. This chemical-origin medication is produced by Fresenius Kabi Nederland B.V.

The trial includes **Folinic Acid**, marketed as Folinezuur Sandoz 10 mg/ml. This is provided as a **solution for injection** and administered via infusion. The dosing regimen allows for a maximum daily dose of 400 mg/m² and a total maximum dose of 4800 mg/m² over the course of the study. Sandoz B.V. is responsible for the production of this chemical-origin active substance.

Lastly, **Fluorouracil**, available as Fluorouracil Accord 50 mg/ml, is utilized in the trial. It is provided as a **solution for injection or infusion** and administered through infusion. The dosing is based on body surface area, with a maximum daily dose of 1200 mg/m² and a total maximum dose of 28800 mg/m² over the treatment period. This chemical-origin medication is manufactured by Accord Healthcare B.V.

Efficacy in the clinical trial titled "Perioperative versus adjuvant FOLFIRINOX for resectable pancreatic cancer: the PREOPANC-3 study" will be assessed primarily through the endpoint of overall survival. This primary endpoint will be evaluated by intention to treat, which involves analyzing all participants based on the group to which they were originally assigned, regardless of the treatment they actually received. The trial aims to investigate whether perioperative mFOLFIRINOX improves overall survival compared to adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer.