Oral Glutamine in the Prevention of Oxaliplatin-induced Neurotoxicity (GLUTOX)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01087658
First received: March 15, 2010
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

Primary Objective:

To assess the benefit of glutamine when added to calcium-magnesium on the occurrence of grade 2, 3 and 4 peripheral sensory neuropathy (PSN) related to oxaliplatin with the National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) scale taking into account the time from start of oxaliplatin at which the first event occurred.

Secondary Objective:

To determine cumulative dose of oxaliplatin and time when the first occurrence of grade 2, 3 or 4 PSN.

To determine the incidence of dose-reductions, dose-delays and discontinuations of oxaliplatin due to PSN grade 3 or 4.

To assess effects of glutamine when added to calcium-magnesium on patients-reported outcomes using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12 items questionnaire (FACT/GOG NTX-12) subscale.

To evaluate the incidence of diarrhea. To determine Progression Free Survival (PFS) in metastatic patients.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Glutamine
Drug: Calcium and Magnesium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Occurence of peripheral sensory neuropathy (PSN) grade 2, 3 and 4 assessed by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) [ Time Frame: Every cycle i.e. 2 or 3 weeks according to the treatment arm ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cumulative dose of oxaliplatin and time of onset when the first PSN grade 2, 3 or 4 occurs [ Time Frame: Every cycle i.e. 2 or 3 weeks according to the treatment arm ] [ Designated as safety issue: No ]
  • Dose-reduction, dose-delay and discontinuation of oxaliplatin due to PSN grade 3 or 4 [ Time Frame: Every cycle i.e. 2 or 3 weeks according to the treatment arm ] [ Designated as safety issue: No ]
  • Patient self-reported neurotoxicity scale for chronic peripheral neuropathy [ Time Frame: Every cycle i.e. 2 or 3 weeks according to the treatment arm ] [ Designated as safety issue: No ]
  • Progression Free Survival / PFS (for metastatic patients) [ Time Frame: Every cycle i.e. 2 or 3 weeks according to the treatment arm ] [ Designated as safety issue: No ]

Enrollment: 200
Study Start Date: February 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glutamine and calcium magnesium

Glutamine 10g p.o. 3-times a day beginning at day -2 for 7 consecutive days during each chemotherapy cycle. 1g of calcium and 1g of magnesium i.v. over 30 minutes just before the chemotherapy and repeated at the same dose after the completion of the oxaliplatine infusion.

All patients will receive an oxaliplatin based chemotherapy with XELOX, FOLFOX-4 or mFOLFOX-6.

Drug: Glutamine
Per os
Drug: Calcium and Magnesium
Intravenous
Active Comparator: Calcium magnesium

1g of calcium and 1g of magnesium i.v. over 30 minutes just before the chemotherapy and repeated at the same dose after the completion of the oxaliplatine infusion.

All patients will receive an oxaliplatin based chemotherapy with XELOX, FOLFOX-4 or mFOLFOX-6.

Drug: Calcium and Magnesium
Intravenous

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  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 surgical sequelae.
  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

Exclusion criteria:

  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 (pyridoxine).
  5. History of known allergy to oxaliplatin or other platinum agents, 5-FU, LV or capecitabine.
  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 or IV),
  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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01087658

Locations
Canada
Investigational Site Number 0001
Greenfield Park, Canada, J4V2H1
Investigational Site Number 124-005
Laval, Canada, H7M3L9
Investigational Site Number 124-007
London, Canada, N6A 4L6
Investigational Site Number 124-014
Moncton, Canada
Investigational Site Number 124-004
Montreal, Canada, H2L 4M1
Investigational Site Number 124-006
Montreal, Canada, H1T 2M4
Investigational Site Number 124-011
Montreal, Canada, H2X 1P1
Investigational Site Number 124010
Montreal, Canada, H2W1S6
Investigational Site Number 124-015
Oshawa, Canada, L1G 2B9
Investigational Site Number 124-012
Ottawa, Canada, K1H8L6
Investigational Site Number 124-003
Quebec, Canada, G1R 2J6
Investigational Site Number 124-017
Rimouski, Canada, G5L5T1
Investigational Site Number 124-002
Toronto, Canada, M5G2M9
Investigational Site Number 124-016
Winnipeg, Canada, R2H2A6
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01087658     History of Changes
Other Study ID Numbers: OXALI_L_03768, U1111-1116-9494
Study First Received: March 15, 2010
Last Updated: June 20, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Colorectal Neoplasms
Chemically-Induced Disorders
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Poisoning
Rectal Diseases
Calcium, Dietary
Oxaliplatin
Antineoplastic Agents
Bone Density Conservation Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014