Phase III Trial on Disease-Free Survival in Resected Pancreatic Ductal Adenocarcinoma Using Oxaliplatin or Gemcitabine-Based Chemotherapy Allocation by Transcriptomic Signature

The primary objective of this study is to evaluate whether **disease-free survival** in patients with resected pancreatic ductal adenocarcinoma (PDAC) is improved when treated with standard adjuvant chemotherapy regimens (oxaliplatin- or gemcitabine-based) allocated based on a treatment-specific signature (TSS), compared to allocation according to standard clinical criteria. This is clinically relevant as it may enhance personalized treatment strategies, potentially leading to better patient outcomes in terms of recurrence prevention.

Secondary objectives include assessing overall survival (median, 3-year survival rate), metastasis-free survival, survival based on targeted signatures (TSS) in test versus control arms, and survival using targeted therapies initially on relapse compared to standard first-line therapies on relapse. These objectives aim to provide a comprehensive understanding of the long-term benefits and effectiveness of personalized treatment approaches in this patient population.

The clinical trial involves participants diagnosed with **resected pancreatic ductal adenocarcinoma**, including variants and pancreatic acinar cell carcinoma. The study population comprises both male and female subjects aged between 18 and 79 years, with a **WHO performance status** of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have a creatinine clearance of at least 50 mL/min and adequate hematologic function, including an absolute neutrophil count of at least 1,500 cells/mm³, platelets of at least 100,000 cells/mm³, and hemoglobin of at least 8 g/L. They must have undergone a macroscopically complete resection (R0 or R1) and be free of significant nausea and vomiting, maintaining adequate oral nutrition of at least 1,500 calories per day. The trial includes individuals who have not received prior radiotherapy or chemotherapy for pancreatic cancer and have fully recovered from surgery, making them eligible to receive chemotherapy. Participants must have public or private health insurance coverage and the ability to understand the nature and consequences of the clinical trial. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **oxaliplatin**- or **gemcitabine**-based chemotherapy in patients with resected pancreatic ductal adenocarcinoma. This is a phase III, randomized, open-label trial that aims to compare disease-free survival when treatment allocation is based on a treatment-specific signature versus standard clinical criteria. The trial will involve a total duration of approximately seven years, with an estimated recruitment start date in September 2024 and an expected end date in July 2031.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as histologically proven pancreatic ductal adenocarcinoma, adequate hematologic function, and a WHO performance status of 0-1. Following successful screening, participants will be randomized to receive either oxaliplatin- or gemcitabine-based chemotherapy. The treatment period will last up to 24 months, with regular follow-up visits to monitor disease progression, treatment response, and any adverse events. The primary endpoint is disease-free survival, defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints include overall survival, metastasis-free survival, and quality of life assessments.

The expected length of participant involvement is up to 24 months, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. Participants will also attend an end-of-study visit to evaluate final outcomes and ensure proper discontinuation of the study treatment. Throughout the trial, safety will be closely monitored, with adverse events graded according to NCI-CTC v.5.0 criteria. The trial's design ensures rigorous assessment of the treatment's efficacy and safety, contributing valuable data to the management of resected pancreatic ductal adenocarcinoma.

The clinical trial involves the administration of several **experimental medications** for the treatment of resected pancreatic ductal adenocarcinoma. **Gemcitabine hydrochloride** is administered in a pharmaceutical form identified as PHF00230MIG. The dosage is set at a maximum of 1000 mg/m² per day, with a total maximum dose of 24000 mg/m² over a treatment period of 24 weeks. The route of administration is intravenous, and the medication is of chemical origin. Participant compliance is monitored through regular assessments of dosing schedules and adherence to the intravenous administration protocol.

**Fluorouracil** is another experimental medication used in this trial, provided in the pharmaceutical form PHF00231MIG. The maximum daily dose is 1200 mg/m², with a total maximum dose of 14400 mg/m² over the same 24-week period. This medication is also administered intravenously and is chemically derived. Compliance monitoring is conducted similarly to ensure adherence to the treatment regimen.

**Oxaliplatin** is included in the trial, with a pharmaceutical form of PHF00230MIG. The maximum daily dose is 85 mg/m², and the total maximum dose is 1020 mg/m² over 24 weeks. It is administered intravenously, and its chemical origin is noted. Participant adherence is tracked through scheduled dosing and administration checks.

**Irinotecan** is administered as a concentrate for solution for infusion, with a maximum daily dose of 150 mg/m² and a total maximum dose of 1800 mg/m² over the 24-week treatment period. The route of administration is intravenous, and the substance is of chemical origin. Compliance is monitored through infusion records and participant follow-up.

**Calcium folinate**, also known as leucovorin calcium, is provided in the pharmaceutical form PHF00231MIG. The maximum daily dose is 400 mg/m², with a total maximum dose of 4800 mg/m² over 24 weeks. It is administered intravenously and is chemically derived. Adherence to the treatment protocol is ensured through regular monitoring of administration schedules.

**Capecitabine** is administered in the pharmaceutical form PHF00009MIG, with a maximum daily dose of 1660 mg/m² and a total maximum dose of 209160 mg/m² over the 24-week period. This medication is taken orally, and its chemical origin is documented. Participant compliance is monitored through pill counts and adherence checks during follow-up visits.

Efficacy in this clinical trial will be assessed primarily through the measurement of **disease-free survival**. This endpoint is defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints include overall survival, metastasis-free survival, overall survival from recurrence, and quality of life, which will be evaluated using the EORTC QLQ C-30 questionnaire. Additionally, safety assessments will be conducted, focusing on Grade 3 and 4 toxicities according to NCI-CTC v.5.0, as well as adverse and serious adverse events.

The trial involves patients with resected pancreatic ductal adenocarcinoma, who will be randomized to receive either oxaliplatin- or gemcitabine-based chemotherapy. The allocation will be based on either standard clinical criteria or a treatment-specific stratification signature. The efficacy parameters will be collected and analyzed at various time points throughout the study, with the estimated end date set for July 14, 2031. The study aims to determine if the use of a treatment-specific signature can improve disease-free survival compared to standard allocation methods.