Clinical trial NCT00305188: Evaluation of the Efficacy of Xaliproden (SR57746A) in Preventing the Neurotoxicity of Oxaliplatin / 5FU/LV Chemotherapy.
Official title: 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
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: 2006-03-21
Enrollment: 879
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: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical evaluation of peripheral sensory neuropathy using the Oxaliplatin specific scale for dose adjustment
timeFrame: Q2W during treatment, Q4W to Q12W during post-treatment follow-up
Secondary outcomes:
measure: Main: response rate using RECIST criteria
timeFrame: Q8W
measure: Other: nerve conduction studies
timeFrame: baseline, end of treatment with oxaliplatin, end of treatment with study drug
measure: Other: progression free survival and survival
timeFrame: Q8W and study period
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
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.