A Trial of Glutamine to Prevent Oxaliplatin Neurotoxicity and a Pharmacokinetic Analysis of Oxaliplatin

A Phase II Trial of Glutamin to Prevent Oxaliplatin Neurotoxicity and a Pharmacokinetic Analysis of Oxaliplatin.

The investigators hypothesize that glutamine significantly reduces the incidence and severity of peripheral neuropathy in patients receiving oxaliplatin for metastatic colorectal cancer, decreases the need for dose reduction of oxaliplatin, and it does not impair oxaliplatin efficacy or pharmacokinetics.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer; Metastasis; Colorectal Tumors; Colorectal Carcinoma; Neoplasms, Colorectal
• Intervention / Treatment: Dietary supplement: Glutamine

Detailed Description

This is a phase II , open-label, non randomized study of oral glutamine administration to evaluate oxaliplatin pharmacokinetics, and to prevent oxaliplatin neurotoxicity in patients with metastatic colorectal cancer.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Study Population: The target population is patients with metastatic colorectal adenocarcinoma who are sufficiently robust to undergo at least 3 cycles of oxaliplatin based chemotherapy (mFOLFOX or XELOX) Sampling Method: Probability Sample.

Inclusion Criteria:

• Patients must hvae metastatic colorectal cancer (stage IV)
• Patients who have been treated with FOLFIRI regimen for metastatic setting may be eligible for this trial
• Patients must be ≥ 18 years
• Patients must have an Eastern Cooperative Oncology Group (EGOC) performance status 0 to 2.
• Patients must have adequate renal function of creatinine < 1.5mg/dL and a creatinine clearance > 45mL/min; patients must have adequate hepatic function with a bilirubin < 1.5mg/dL and AST (normal range 0-14 U/L) and ALT (normal range 0-49 U/L); and patients must have adequate bone marrow function with absolute neutrophil count (ANC) ≥ 1,500/цL and platelets ≥ 100,000/цL and a hemoglobin ≥ 10g/d.
• Patients must be willing and able to comply with the study protocol for the duration of the study.
• Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• The investigator is requested to advise the patient how to achieve an adequate contraception
• Life expectancy longer than 6 months

Exclusion Criteria:

• Patients who have received oxaliplatin previously
• Patients with previous of current diagnosis of peripheral sensory neuropathy
• Patients who have tested positive for HIV
• Patients with other significant medical, psychiatric disorders that, in the opinion of the investigator, will exclude the patient from the study for compliance or safety reasons.
• Patients who cannot swallow
• History of known allergy to oxaliplatin or other platinum compounds, to 5-FU, to LV, glutamine or to any ingredients in the formulations of the containers
• Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
• Pernicious anemia or other megaloblastic anemia with vitamin B12 deficiency
• Patients with concomitant treatment with drugs/ingredients reported to have a potential activity to prevent PSN
• Patients who haven't successfully completed local therapy for previously treated CNS metastases and who haven't been discontinued with corticosteroid for > 4wks before starting chemotherapy. Patients with asymptomatic brain mets. who have no evidence of midline shift on CT/ MRI may be enrolled without initiation of local therapy for the CNS mets. Repeat scan must be preformed < 4wks to ensure no progression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dietary Supplement; Arm A: At cycle 2, patients will be randomized to receive for 6 days- Glutamine 30g/day during cycle 2 and glutamine 40g/day during cycle 3	Dietary supplement: Glutamine; Glutamine- During the first cycle of oxaliplatin based combination therapy (mFOLFOX 6 or XELOX) no patient will receive glutamine. At cycle 2, patients will be randomized to receive for 6 days either : Glutamine 30g/day during cycle 2 and glutamine 40g/day during cycle 3 (ARM A) or glutamine 40g/day at cycle 2 and glutamine 30g/day at cycle 3 (Arm B).; Other Names: L-glutamine
Experimental: Dietary supplement; Arm B: At cycle 2, patients will be randomized to receive for 6 days: Glutamine 40g/day at cycle 2 and glutamine 30g/day at cycle 3.	Dietary supplement: Glutamine; Glutamine- During the first cycle of oxaliplatin based combination therapy (mFOLFOX 6 or XELOX) no patient will receive glutamine. At cycle 2, patients will be randomized to receive for 6 days either : Glutamine 30g/day during cycle 2 and glutamine 40g/day during cycle 3 (ARM A) or glutamine 40g/day at cycle 2 and glutamine 30g/day at cycle 3 (Arm B).; Other Names: L-glutamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate potential pharmacokinetic interactions between oxaliplatin and glutamine at 30g and 40g in patients with metastatic colorectal cancer.	Post cycle 2 and cycle 3

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate effects of glutamine supplementation on neuropathy and diarrhea related to oxaliplatin, and on dose reductions and in patients with metastatic colorectal cancer.	Post cycle 2 to 30-day follow-up visit
To compare the toxicity profile of glutamine and FOLFOX to historical data.	Post cycle 2 to 30-day follow-up visit.

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Collaborators: Cross Cancer Institute
• Investigators: Study Chair: Michael Sawyer, MD, Alberta Health services

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): September 1, 2012
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 2, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Estimate): February 24, 2016
• Last Update Submitted That Met QC Criteria: February 23, 2016
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: oxaliplatin; adverse effects; glutamine
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Poisoning; Colorectal Neoplasms; Neurotoxicity Syndromes
• Other Study ID Numbers: 25070

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No