Oral Glutamine in the Prevention of Oxaliplatin-induced Neurotoxicity

NCT01087658 | Completed Phase 3

• 2 other identifiers: OXALI_L_03768U1111-1116-9494
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 14

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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)

  Every cycle i.e. 2 or 3 weeks according to the treatment arm

Secondary Outcomes (4)

• Cumulative dose of oxaliplatin and time of onset when the first PSN grade 2, 3 or 4 occurs

  Every cycle i.e. 2 or 3 weeks according to the treatment arm

• Dose-reduction, dose-delay and discontinuation of oxaliplatin due to PSN grade 3 or 4

  Every cycle i.e. 2 or 3 weeks according to the treatment arm

• Patient self-reported neurotoxicity scale for chronic peripheral neuropathy

  Every cycle i.e. 2 or 3 weeks according to the treatment arm

• Progression Free Survival / PFS (for metastatic patients)

  Every cycle i.e. 2 or 3 weeks according to the treatment arm

Study Arms (2)

Glutamine and calcium magnesium

EXPERIMENTAL

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; Drug: Calcium and Magnesium

Calcium magnesium

ACTIVE COMPARATOR

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

Interventions

Glutamine DRUG

Per os

Glutamine and calcium magnesium

Calcium and Magnesium DRUG

Intravenous

Calcium magnesium; Glutamine and calcium magnesium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (14)

Investigational Site Number 0001

Greenfield Park, J4V2H1, Canada

Location

Investigational Site Number 124-005

Laval, H7M3L9, Canada

Location

Investigational Site Number 124-007

London, N6A 4L6, Canada

Location

Investigational Site Number 124-014

Moncton, Canada

Location

Investigational Site Number 124-006

Montreal, H1T 2M4, Canada

Location

Investigational Site Number 124-004

Montreal, H2L 4M1, Canada

Location

Investigational Site Number 124010

Montreal, H2W1S6, Canada

Location

Investigational Site Number 124-011

Montreal, H2X 1P1, Canada

Location

Investigational Site Number 124-015

Oshawa, L1G 2B9, Canada

Location

Investigational Site Number 124-012

Ottawa, K1H8L6, Canada

Location

Investigational Site Number 124-003

Québec, G1R 2J6, Canada

Location

Investigational Site Number 124-017

Rimouski, G5L5T1, Canada

Location

Investigational Site Number 124-002

Toronto, M5G2M9, Canada

Location

Investigational Site Number 124-016

Winnipeg, R2H2A6, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Glutamine; Calcium; Magnesium

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Metals, Light

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: June 21, 2013

Record last verified: 2013-06

Locations

CA (14)