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

Colorectal Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305188
• Other study ID #: EFC5505
• Secondary ID: EUDRACT : 2005-0
• Status: Completed
• Phase: Phase 3
• First received: March 20, 2006
• Last updated: December 16, 2010
• Start date: December 2005
• Est. completion date: October 2009

Study information

• Verified date: December 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: National Health Service
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 879
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Carcinoma
• Colorectal Neoplasms
• Metastases
• Neurotoxicity Syndromes

Intervention

Drug:
• xaliproden (SR57746A)
oral administration
• Placebo
oral administration
• oxaliplatin
in combination with 5-Fluorouracil and Leucovorin

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
Germany	Sanofi-Aventis Administrative Office	Berlin
Hungary	Sanofi-Aventis Administrative Office	Budapest
Italy	Sanofi-Aventis Administrative Office	Milano
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Spain	Sanofi-Aventis Administrative Office	Barcelona
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Germany,  Hungary,  Italy,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Main: response rate using RECIST criteria		Q8W	No
Secondary	Other: nerve conduction studies		baseline, end of treatment with oxaliplatin, end of treatment with study drug	No
Secondary	Other: progression free survival and survival		Q8W and study period	No