Evaluation of the Efficacy of Xaliproden (SR57746A) in Preventing the Neurotoxicity of Oxaliplatin / 5FU/LV Chemotherapy.

Study Overview
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Brief Summary
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Primary Objective : Compare the risk of occurrence of Grade3-4 cumulative peripheral sensory neuropathy (PSN) relative to cumulative dose of oxaliplatin between treatment group and placebo group. Main Secondary Objective : Compare the response rate (RR) between treatment group and placebo group in order to ensure that the efficacy of the chemotherapy is not compromised by the addition of xaliproden to the chemotherapeutic regimen. Other Secondary Objectives : study of the neurotoxicity parameters (Duration of oxaliplatin-induced PSN (G2,3,4); overall incidence of PSN during treatment; dose of onset of PSN ; incidence of dose-reduction and dose delay due to PSN; incidence of oxaliplatin treatment discontinuation due to PSN; change in Nerve Conduction Studies (NCS)) ; study of the safety profile (other than PSN) ; study of the chemotherapy efficacy (progression free survival, overall survival).

Official Title
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A Multicenter, Randomized Double-blind Placebo Controlled Phase III Study of the Efficacy of Xaliproden in Preventing the Neurotoxicity of Oxaliplatin in First-line Treatment of Patients With Metastatic Colorectal Cancer Treated With Oxaliplatin / 5-FU/LV

Conditions
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Metastases, Colorectal Neoplasms, Colorectal Carcinoma

Intervention / Treatment
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* Drug: Xaliproden (SR57746A)
* Drug: Placebo
* Drug: Oxaliplatin
* Drug: 5-Fluorouracil
* Drug: Leucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main inclusion criteria : Histologically or cytologically-proven metastatic cancer of the colon or rectum. Metastatic disease not amenable to potentially curative treatment (eg: inoperable metastatic disease). Male or female aged >18 years. WHO Performance Status (PS) : 0 or 1. Measurable disease. No prior chemotherapeutic regimen for metastatic disease. Disease-free interval from end of adjuvant therapy of at least 6 months (1 year if oxaliplatin was part of the adjuvant therapy). Prior radiotherapy is permitted if it was not administered to target lesions identified for this study - unless progression within the radiation portal is documented - and provided it has been completed at least 3 weeks before randomization. Signed written informed consent prior to study entry. Exclusion Criteria: Main exclusion criteria : Any condition or past medical history that contra-indicates treatment with oxaliplatin and 5-FU, as reported in approved labeling information. Received chemotherapeutic agents other than 5-FU, LV, Levamisole, irinotecan, capecitabine, oxaliplatin as part of adjuvant therapy. Peripheral neuropathy >Grade 1. Concomitant treatments with drugs/ingredients reported to have a potential activity in preventing peripheral sensory neuropathy. Concurrent active cancer originating from a primary site other than colon or rectum. Presence of any symptom suggesting brain metastasis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xaliproden (SR57746A)<br> | Drug: Xaliproden (SR57746A)<br>* oral administration<br>Drug: Oxaliplatin<br>* IV administration<br>Drug: 5-Fluorouracil<br>* IV administration<br>* Other names: 5-FU;Drug: Leucovorin<br>* IV administration<br>* Other names: LV;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* oral administration<br>Drug: Oxaliplatin<br>* IV administration<br>Drug: 5-Fluorouracil<br>* IV administration<br>* Other names: 5-FU;Drug: Leucovorin<br>* IV administration<br>* Other names: LV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evaluation of peripheral sensory neuropathy using the Oxaliplatin specific scale for dose adjustment |  | Q2W during treatment, Q4W to Q12W during post-treatment follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main: response rate using RECIST criteria |  | Q8W | 
| Other: nerve conduction studies |  | baseline, end of treatment with oxaliplatin, end of treatment with study drug | 
| Other: progression free survival and survival |  | Q8W and study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurotoxicity syndromes, Paresthesia, Oxaliplatin, Xaliproden