Comparison of Intra-Arterial vs. Intravenous Oxaliplatin with LV5FU2 ± Irinotecan in First-Line Treatment of Liver-Restricted Metastatic Colorectal Cancer

The primary objective of this study is to compare **progression-free survival** between intra-arterial and intravenous administration of **oxaliplatin** in patients with metastatic colorectal cancer restricted to the liver. This comparison is clinically relevant as it may inform treatment strategies that optimize patient outcomes by potentially enhancing the efficacy of chemotherapy delivery methods. Progression is assessed according to RECIST v1.1 criteria and the investigator's evaluation.

Secondary objectives include: - Evaluation of toxicities according to NCI-CTC v4.0. - Assessment of the best response under treatment and radiological progression-free survival after central review of X-rays. - Determination of the best response obtained under treatment according to the investigator. - Measurement of overall survival (median). - Analysis of hepatic progression-free survival (median). - Evaluation of quality of life using QLQ-C30. - Assessment of early tumor shrinkage (response > 20%) at 8 weeks. - Determination of the depth of response. - Calculation of the secondary resection rate. - Evaluation of histological response in cases of secondary resection. - Monitoring of the evolution of the tumoral marker (CEA). - Analysis of progression-free survival under 'active' treatment. - Subgroup analysis on patients treated with intra-arterial versus intravenous oxaliplatin in combination with bi-chemotherapy and tri-chemotherapy.

The clinical trial involves participants diagnosed with **colon cancer and rectal cancer with liver metastasis**. The study population includes both male and female subjects, aged 18 years and older, with a performance status of 2 or less according to the World Health Organization (WHO) scale. Participants are required to have histologically confirmed colorectal adenocarcinoma with hepatic metastases and must meet specific laboratory criteria, including total bilirubin levels below 25 μmol/L and creatinine clearance above 50 mL/min. The trial does not include individuals with prior chemotherapy, except for perioperative or adjuvant chemotherapy discontinued for more than 12 months, and the first course of FOLFOX or mFOLFIRINOX IV without targeted therapy before randomization. The study population was selected based on these criteria, and participants must have a life expectancy greater than three months. The trial includes a vulnerable population, and the sponsor has not provided the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **oxaliplatin** administered either intra-arterially or intravenously in combination with LV5FU2 ± Irinotecan and targeted therapy for the first-line treatment of metastatic colorectal cancer restricted to the liver. This is a randomized, double-blind, controlled trial with an estimated duration from December 23, 2016, to February 27, 2026. The primary objective is to compare radiological and/or clinical progression-free survival between the two administration routes, assessed according to RECIST v1.1 criteria and investigator evaluation. Secondary endpoints include grading of adverse events, overall survival, hepatic progression-free survival, early tumor shrinkage, depth of response, secondary resection rate, histological response evaluation, marker evolution, quality of life, and progression-free survival under active treatment.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven colorectal adenocarcinoma with hepatic metastasis, specific laboratory values, and known RAS mutation status. Follow-up visits will occur before each chemotherapy cycle to assess adverse events and treatment response. The end-of-study visit will evaluate the overall outcomes and any long-term effects. The expected length of participant involvement is determined by the treatment regimen and progression status, with early termination possible if significant adverse events occur or if the participant withdraws consent.

The clinical trial involves the administration of **Eloxatine**, a pharmaceutical product containing the active substance **oxaliplatin**. Eloxatine is provided as a **solution for infusion** with a concentration of 5 mg/ml. The medication is manufactured by Sanofi Winthrop Industrie and is authorized for use in France. The trial utilizes two different administration routes for Eloxatine: intra-arterial and intravenous. The maximum daily dose for both routes is 85 mg/m², and the treatment period is limited to one day. The intra-arterial administration is specifically used in arms A and C of the trial, while the intravenous route is employed in arms B and D. The primary objective of the trial is to compare the progression-free survival between these two administration methods in patients with metastatic colorectal cancer restricted to the liver.

In addition to Eloxatine, the trial protocol includes the use of standard-of-care therapies such as LV5FU2, with or without irinotecan, and targeted therapy. These non-experimental treatments are administered according to established clinical guidelines and are intended to provide a comprehensive therapeutic approach alongside the experimental administration of oxaliplatin. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen and to accurately assess the efficacy and safety of the interventions.

Efficacy in the clinical trial titled "PRODIGE 49 - OSCAR" will be assessed primarily through the comparison of **progression-free survival** (PFS) between two administration routes of **oxaliplatin**: intra-arterial (arms A and C) and intravenous (arms B and D). The progression will be evaluated using the RECIST v1.1 criteria and investigator assessments. Secondary endpoints include the grading of adverse events according to NCI CTCAE v4.0 before each chemotherapy cycle, evaluation of the best response under treatment based on RECIST v1.1, and overall survival, defined as the time from treatment initiation to death from any cause. Additional secondary endpoints involve hepatic progression-free survival, early tumor shrinkage at 8 weeks, depth of response, secondary resection rate, histological response evaluation, marker evolution during treatment, quality of life, and progression-free survival under active treatment. These parameters will be measured and analyzed at specified intervals throughout the trial to determine the efficacy of the treatment regimens.