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

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

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

Study Overview

• Status: Terminated
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Placebo; Drug: Xaliproden

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Frankfurt, Germany
    • Sanofi-Aventis Administrative Office
• Greece
  • Kallithea, Greece
    • Sanofi-Aventis Administrative Office
• Italy
  • Milan, Italy
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Jean-Philippe Aussel, Sanofi

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 17, 2008
• First Submitted That Met QC Criteria: January 28, 2008
• First Posted (Estimate): January 29, 2008

Study Record Updates

• Last Update Posted (Estimate): May 5, 2016
• Last Update Submitted That Met QC Criteria: April 6, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Xaliproden
• Other Study ID Numbers: XALIP_C_02090