Evaluation of Neoadjuvant FOLFIRINOX Versus Gemcitabine-Based Chemoradiotherapy in Borderline Resectable Pancreatic Cancer

The primary objective of this study is to evaluate the **effectiveness** of neoadjuvant **FOLFIRINOX** followed by surgery in improving overall survival and quality of life compared to neoadjuvant chemoradiotherapy followed by surgery and adjuvant **gemcitabine** in patients with non-metastatic (borderline) resectable pancreatic cancer. This is assessed in an intention-to-treat setting. The clinical relevance of this objective lies in determining the optimal preoperative treatment strategy to enhance patient outcomes in terms of survival and quality of life, which are critical factors in the management of pancreatic cancer.

The clinical trial involves participants diagnosed with **non-metastatic (borderline) resectable pancreatic cancer**. The study population includes both male and female subjects, aged 18 years and older, who are in good general health as indicated by a WHO performance status of 0 or 1. Participants must have the ability to undergo surgery, chemoradiotherapy, and chemotherapy. The trial does not include vulnerable populations. The sponsor has not provided the total number of participants. Selection criteria require histologically or cytologically confirmed pancreatic cancer, a (borderline) resectable tumor without metastatic disease, and adequate hematological and renal function. Lifestyle considerations such as diet and physical activity are not specified. The trial population was selected based on these criteria to ensure the safety and efficacy of the interventions being studied.

The clinical trial is designed to evaluate the **effectiveness** of neoadjuvant FOLFIRINOX compared to neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine in patients with non-metastatic (borderline) resectable pancreatic cancer. This is a multicenter, randomized, double-blind, controlled Phase III study. The trial aims to determine whether the FOLFIRINOX regimen improves overall survival and quality of life in an intention-to-treat setting. The primary endpoint is overall survival, with the trial expected to conclude by June 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically or cytologically confirmed pancreatic cancer, WHO performance status of 0 or 1, and adequate organ function. Following randomization, participants will receive treatment over a maximum period of 26 to 44 weeks, depending on the regimen assigned. Study visits will include regular follow-up assessments to monitor treatment response and adverse events. The end-of-study visit will occur after the completion of the treatment period to evaluate the final outcomes.

The expected length of participant involvement is up to 44 weeks, with conditions for early termination including significant adverse events, disease progression, or withdrawal of consent. Participants will receive either FOLFIRINOX or gemcitabine-based chemoradiotherapy, with the specific regimen determined by random assignment. The trial will adhere to rigorous ethical standards, ensuring that all procedures are conducted in compliance with regulatory requirements and guidelines.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Irinotecan hydrochloride trihydrate** is provided as a concentrate for solution for infusion, marketed under the name "Irinotecan HCl-trihydraat Fresenius Kabi 20 mg/ml." The maximum daily dose is 180 mg/m², with a total maximum dose of 1440 mg/m² over a treatment period of up to 26 weeks. The administration route is via infusion.

**Folinic acid** is administered as a solution for injection, known commercially as "Folinezuur Sandoz 10 mg/ml." The maximum daily dose is 400 mg/m², with a total maximum dose of 3200 mg/m², also over a 26-week period. This medication is delivered through infusion.

**Oxaliplatin** is provided as a concentrate for solution for infusion, under the name "Oxaliplatine Fresenius Kabi 5 mg/ml." The maximum daily dose is 85 mg/m², with a total maximum dose of 680 mg/m², administered over a 26-week period. The route of administration is infusion.

**Gemcitabine hydrochloride** is available as a concentrate for solution for infusion, marketed as "Gemcitabine Sandoz 40 mg/ml." The maximum daily dose is 1000 mg/m², with a total maximum dose of 19000 mg/m², administered over a period of up to 44 weeks. The administration is conducted via infusion.

**Fluorouracil** is provided as a solution for injection or infusion, under the commercial name "Fluorouracil Accord 50 mg/ml." The maximum daily dose is 1600 mg/m², with a total maximum dose of 22400 mg/m², administered over a 26-week period. The administration route is either injection or infusion.

All medications are chemically derived and are administered via infusion, with the exception of Fluorouracil, which can also be injected. Participant compliance is monitored throughout the trial to ensure adherence to the dosing schedules. The trial aims to evaluate the effectiveness of these treatments in patients with borderline resectable pancreatic cancer, comparing neoadjuvant FOLFIRINOX followed by surgery to neoadjuvant chemoradiotherapy followed by surgery and adjuvant gemcitabine.

Efficacy in this clinical trial will be assessed primarily through the endpoint of overall survival in patients with (borderline) resectable pancreatic cancer. The trial aims to compare the effectiveness of neoadjuvant FOLFIRINOX followed by surgery against neoadjuvant chemoradiotherapy followed by surgery and adjuvant **gemcitabine**. The primary endpoint, overall survival, will be measured to determine the impact of the treatment regimens on patient longevity.