Clinical trial NCT00272051: XENOX - Evaluation of the Efficacy of Xaliproden in Reducing the Neurotoxicity of the Oxaliplatin + 5-FU/LV Chemotherapy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastases
Colorectal Neoplasms
Colorectal Carcinoma
Keywords: Neurotoxicity syndromes
Paresthesia
Oxaliplatin
Xaliproden
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-01-04
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Clinical evaluation of peripheral sensory neuropathy using the Oxaliplatin specific scale for dose adjustment : Q2W ; response rate using RECIST criteria : Q8W
Secondary outcomes:
measure: Safety : Q2W ; Nerve conduction studies : Baseline + cycle 12 ; Progression Free Survival : Q8W ; Survival
Other outcomes:
Locations:
Study officials:
affiliation: Hôpital de Bicêtre - Le Kremlin-Bicêtre - France
name: Gérard SAID, MD
role: STUDY_CHAIR
References:
citation: Abdel-Rahman O. Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Dec;18(4):e385-e393. doi: 10.1016/j.clcc.2019.07.005. Epub 2019 Jul 15.
citation: Abdel-Rahman O. Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Jun;18(2):110-115.e2. doi: 10.1016/j.clcc.2018.12.006. Epub 2018 Dec 28.