A Multicentre, Randomized, Open-label, Phase III Study Comparing the Efficacy of Oral Glutamine and Calcium-magnesium With Calcium-magnesium Alone in the Prevention of Oxaliplatin-induced Neurotoxicity in Patients With Colorectal Cancer Treated With Oxaliplatin in Adjuvant or 1st Line Metastatic Settings.
1. Histologically- or cytologically- proven adenocarcinoma of the colon or rectum.
2. Disease either in adjuvant or 1st line metastatic setting.
3. Eastern Cooperation Oncology Group (ECOG) performance status inferior or equal to 2.
4. At least 4 weeks following any major surgical procedure(s) and recovery from any
5. Electrocardiogram (ECG) with no acute or recent changes within limit of normal range,
and not presenting abnormalities contraindicating the proposed chemotherapy.
6. Adequate liver and kidney function:
- Total bilirubin inferior to 1.5 ULN
- Serum creatinine inferior to 150 umol/L
- Creatinine clearance (ClCr) superior to 45 mL/min
- ALT/AST inferior to 3 ULN
- Alkaline phosphatase inferior or equal to 2 ULN, unless liver metastases are
present and documented at baseline by Computed Tomography (CT) or Magnetic
Resonance Imaging (MRI) scans (inferior or equal to 3,5 ULN in that case).
7. Adequate hematological function:
- Neutrophils superior or equal to 1.5 x 109/L
- Platelet count superior or equal to 100 x 109/L
- Hemoglobin superior to 9 g/dL
1. Any condition or past medical history that contra-indicates treatment with
oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) or capecitabine as reported in
the approved labeling information.
2. Previous oxaliplatin-based chemotherapy.
3. Previous or current diagnosis of PSN.
4. Concomitant treatments with drugs/ingredients reported to have a potential activity
in preventing PSN: carbamazepine, amitriptyline, gabapentin, phenytoin, glutathione,
alpha-lipoic acid, celecoxib, amifostine, venlafaxine, vitamin B1 (thiamine), B6
5. History of known allergy to oxaliplatin or other platinum agents, 5-FU, LV or
6. History of known allergy to glutamine or to calcium-magnesium.
7. Participation in another clinical trial with any investigational drug within 30 days
prior to study screening.
8. Uncontrolled intercurrent illness: e.g. high blood pressure, unstable angina,
symptomatic congestive heart failure (New York Heart Association Classification III
9. Serious cardiac arrhythmia, diabetes, or active infection.
10. Concurrent active cancer originating from a primary site other than colon or rectum.
11. Presence of any symptom suggesting brain metastasis.
12. Patients who are pregnant or breast-feeding
13. Patients (males and females) with reproductive potential not implementing accepted
and effective method of contraception
14. For patient who will receive Bevacizumab: Bevacizumab is contraindicated in patients
with known hypersensitivity to any components of the product to Chinese hamster ovary
cell product or other recombinant human or humanized antibodies
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.