XENOX - Evaluation of the Efficacy of Xaliproden in Reducing the Neurotoxicity of the Oxaliplatin + 5-FU/LV Chemotherapy

A Multicenter Randomized Dble-Blind Placebo Controlled Phase III Study of the Efficacy of Xaliproden in Reducing the Neurotoxicity of the Oxaliplatin and 5-FU/LV Combination in First-Line Treatment of Patients With Metastatic Colorectal Carcinoma(MCRC)

Purpose of the trial is to evaluate the efficacy of Xaliproden in reducing the neurotoxicity of the Oxaliplatin and 5-FU/LV chemotherapy, in patients with metastatic colorectal carcinomaPrimary objectives : Compare the risk of occurence of grade 3-4 peripheral sensory neuropathy relative to the cumulative dose of Oxaliplatin between treatment group and placebo group ; Compare the response rate between treatment group and placebo group.Secondary objectives : neurotoxicity parameters (overall incidence, time and dose to onset, time to recovery, change in the sensory action potentials) ; antitumoral efficacy (progression-free survival, overall survival) ; safety profile.

Inclusion Criteria:

• Histologically or cytologically proven adenocarcinoma of the colon or the rectum
• age > 18 years
• WHO performance status : 0,1,2
• Signed written informed consent prior to study entry
• Disease stage : metastatic disease not amenable to potentially curative treatment (eg : inoperable metastatic disease)
• Measurable disease
• No prior chemotherapeutic regimen for metastatic disease ; prior adjuvant chemotherapy allowed (disease free interval from end of adjuvant therapy of at least 6 months)
• Prior radiotherapy permitted, if completed at least 3 weeks before randomization, and if not administered to target lesions identified for the study

Exclusion Criteria:

• Chemotherapeutic agents other than 5-FU/LV or 5-FU/Levamizole as part of adjuvant therapy
• Prior therapy with Oxaliplatin
• History of cardiac toxicities under 5-FU/LV therapy or myocardial infarction within the 6 months before study entry ; Known Dihydropyrimidine Dehydrogenase deficiency
• History of intolerance to appropriate antiemetics
• Concurrent active cancer originating from a primary site other than colon or rectum
• Presence of any symptom suggesting brain metastasis
• Known peripheral neuropathy
• Interstitial pneumonia or extensive and symptomatic fibrosis of the lung
• Allergy to Xaliproden/excipients