Role of Xaliproden on Recovery Rate From Severe Neuropathy in Patients Who Have Completed Adjuvant Chemotherapy With Oxaliplatin Based Regimens

Study Overview
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Brief Summary
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Primary objective: To assess the effect of xaliproden hydrochloride (xaliproden) 1 mg per oral daily on the rate of complete resolution of peripheral sensory neuropathy (PSN) at 6 months, following randomization, after the completion of oxaliplatin-based adjuvant chemotherapy for colon cancer. Secondary objective: To assess the effect of xaliproden on patient-reported outcomes using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale (FACT/GOG NTX-12 subscale). To assess the effect of xaliproden on the rate of at least partial recovery of grade > 2 PSN at 6 months To assess the effects of xaliproden on the time to complete recovery from PSN To evaluate the safety profile of xaliproden

Official Title
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A Multi-center, Randomized, Double Blind, Placebo Controlled Phase III Study to Assess the Efficacy of Xaliproden in Patients With Oxaliplatin-induced Peripheral Sensory Neuropathy (PSN) Following Adjuvant Chemotherapy for Colon Cancer

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Placebo
* Drug: Xaliproden


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed an oxaliplatin-containing chemotherapy regimen post complete surgical removal of primary colon tumor no later than 6 weeks before randomization; Have Grade ≥ 1 PSN, as defined by the NCI-CTCAE version 3.0 Have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2; Blood tests within 14 days prior to randomization: (a) AST (SGOT) and ALT (SGPT) ≤2 x upper limit of normal (ULN); (b) serum creatinine ≤1.5 x ULN; (c)HbA1c ≤7%; (d) neutrophils ≥1.5x10^9/L ; (e) platelets ≥50x10^9/L; (f) Serum D-dimer within normal limits Exclusion Criteria: Pre-existing peripheral neuropathy prior to treatment with oxaliplatin Receiving any further anti-cancer treatment History of any recent (≤1 year) thrombo-embolic events and current clinical evidence of thrombo-embolism Unstable cardiac disease History of significant neurological or psychiatric disorders including dementia or seizures, Active uncontrolled infection Active disseminated intravascular coagulation Other serious underlying medical conditions which could impair the ability of the patient to participate in the study; Use of antidepressant/antiepileptic medication (for the treatment of PSN), unless commenced before informed consent form signed. The addition of these medications (for the treatment of PSN) once the patient has consented is not allowed Concurrent treatment with any other experimental drugs Pregnant or breast-feeding women; Women of childbearing potential must be protected by effective contraceptive methods of birth control. Post-menopausal women must have been amenorrheic for at least 12 months to be considered as having non-childbearing potential Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Those conditions should be assessed with the patient before registration in the trial. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Xaliproden matching placebo. 1 capsule per day for 6 months or until resolution of PSN (whichever comes first).<br>|
| Experimental: Xaliproden<br> | Drug: Xaliproden<br>* 1.0 mg capsule. 1 capsule per day for 6 months or until resolution of PSN (whichever comes first).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological sensory assessment using the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE, Version 3.0) |  | inclusion, 3 and 6 months and at the 9 and 12 moth follow-up visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FACT/GOG NTX-12 subscale |  | AT inclusion and subsequently monthly until month 12 | 
| Hematological and biochemical testing |  | At inclusion, 3 & 6 months | 
| AE graded with NCI-CTCAE (Version 3.0) and coded using Medical Dictionary for Regulatory Activities (MedDRA, version 9.1) |  | During the whole study period (including follow-up) |