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

Primary Purpose

Colorectal Neoplasms

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Glutamine
Calcium and Magnesium
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 0001
  • Investigational Site Number 124-005
  • Investigational Site Number 124-007
  • Investigational Site Number 124-014
  • Investigational Site Number 124-006
  • Investigational Site Number 124-004
  • Investigational Site Number 124010
  • Investigational Site Number 124-011
  • Investigational Site Number 124-015
  • Investigational Site Number 124-012
  • Investigational Site Number 124-003
  • Investigational Site Number 124-017
  • Investigational Site Number 124-002
  • Investigational Site Number 124-016

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Glutamine and calcium magnesium

Calcium magnesium

Arm Description

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.

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.

Outcomes

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)

Secondary Outcome Measures

Cumulative dose of oxaliplatin and time of onset when the first PSN grade 2, 3 or 4 occurs
Dose-reduction, dose-delay and discontinuation of oxaliplatin due to PSN grade 3 or 4
Patient self-reported neurotoxicity scale for chronic peripheral neuropathy
Progression Free Survival / PFS (for metastatic patients)

Full Information

First Posted
March 15, 2010
Last Updated
June 20, 2013
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01087658
Brief Title
Oral Glutamine in the Prevention of Oxaliplatin-induced Neurotoxicity
Acronym
GLUTOX
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Glutamine and calcium magnesium
Arm Type
Experimental
Arm Description
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.
Arm Title
Calcium magnesium
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Glutamine
Intervention Description
Per os
Intervention Type
Drug
Intervention Name(s)
Calcium and Magnesium
Intervention Description
Intravenous
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Patient self-reported neurotoxicity scale for chronic peripheral neuropathy
Time Frame
Every cycle i.e. 2 or 3 weeks according to the treatment arm
Title
Progression Free Survival / PFS (for metastatic patients)
Time Frame
Every cycle i.e. 2 or 3 weeks according to the treatment arm

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Histologically- or cytologically- proven adenocarcinoma of the colon or rectum. Disease either in adjuvant or 1st line metastatic setting. Eastern Cooperation Oncology Group (ECOG) performance status inferior or equal to 2. At least 4 weeks following any major surgical procedure(s) and recovery from any surgical sequelae. Electrocardiogram (ECG) with no acute or recent changes within limit of normal range, and not presenting abnormalities contraindicating the proposed chemotherapy. 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). 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: 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. Previous oxaliplatin-based chemotherapy. Previous or current diagnosis of PSN. 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). History of known allergy to oxaliplatin or other platinum agents, 5-FU, LV or capecitabine. History of known allergy to glutamine or to calcium-magnesium. Participation in another clinical trial with any investigational drug within 30 days prior to study screening. Uncontrolled intercurrent illness: e.g. high blood pressure, unstable angina, symptomatic congestive heart failure (New York Heart Association Classification III or IV), Serious cardiac arrhythmia, diabetes, or active infection. Concurrent active cancer originating from a primary site other than colon or rectum. Presence of any symptom suggesting brain metastasis. Patients who are pregnant or breast-feeding Patients (males and females) with reproductive potential not implementing accepted and effective method of contraception 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 0001
City
Greenfield Park
ZIP/Postal Code
J4V2H1
Country
Canada
Facility Name
Investigational Site Number 124-005
City
Laval
ZIP/Postal Code
H7M3L9
Country
Canada
Facility Name
Investigational Site Number 124-007
City
London
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Investigational Site Number 124-014
City
Moncton
Country
Canada
Facility Name
Investigational Site Number 124-006
City
Montreal
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Investigational Site Number 124-004
City
Montreal
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
Investigational Site Number 124010
City
Montreal
ZIP/Postal Code
H2W1S6
Country
Canada
Facility Name
Investigational Site Number 124-011
City
Montreal
ZIP/Postal Code
H2X 1P1
Country
Canada
Facility Name
Investigational Site Number 124-015
City
Oshawa
ZIP/Postal Code
L1G 2B9
Country
Canada
Facility Name
Investigational Site Number 124-012
City
Ottawa
ZIP/Postal Code
K1H8L6
Country
Canada
Facility Name
Investigational Site Number 124-003
City
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
Investigational Site Number 124-017
City
Rimouski
ZIP/Postal Code
G5L5T1
Country
Canada
Facility Name
Investigational Site Number 124-002
City
Toronto
ZIP/Postal Code
M5G2M9
Country
Canada
Facility Name
Investigational Site Number 124-016
City
Winnipeg
ZIP/Postal Code
R2H2A6
Country
Canada

12. IPD Sharing Statement

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Oral Glutamine in the Prevention of Oxaliplatin-induced Neurotoxicity

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