Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00195013
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 125
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Patients with breast cancer receiving paclitaxel chemotherapy who have mild symptoms of peripheral neuropathy will receive glutamine or placebo to try and improve symptoms.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Neuropathy; Breast Cancer	Drug: glutamine; Drug: Placebo	Phase 3

Detailed Description

1. Determine whether oral glutamine supplementation can reduce the symptoms and signs of peripheral neuropathy.

2. Determine whether alterations in the symptoms and signs of peripheral neuropathy are correlated with an alteration of circulating nerve growth factor or insulin-like growth factor levels.

3. Assess whether oral glutamine affects circulating nerve growth factor or insulin-like growth factor levels.

4. Assess whether glutamine interferes with paclitaxel pharmacokinetics

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Placebo-controlled Trial of Glutamine to Reduce the Signs and Symptoms of Peripheral Neuropathy in Breast Cancer Patients With a Mild Peripheral Neuropathy Receiving Paclitaxel Chemotherapy
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glutamine 10 grams three times a day (orally) for four days and then stop	Drug: glutamine; 10 grams three times a day (orally) for four days and then stop; Other Names: NutreStore
Placebo Comparator: Placebo 10 grams three times a day (orally) for four days and then stop	Drug: Placebo; 10 grams three times a day (orally) for four days and then stop; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Change in Peripheral Neuropathy Score [Duration of study, approximately 10 weeks per subject]

   Used the clinical total neuropathy score scale (TNSc). The presence of sensory, motor, pin sensibility, vibration sensibility, DTR, autonomic symptoms was assessed. For each item, the possible score ranged between 0 (normal) and 4 (worst possible result). Outcomes calculated as neuropathy score value at 10 Weeks minus neuropathy score value at Baseline. Increased score value indicates increased neuropathy severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed breast cancer, Stage I, II, III or IV or other solid tumors.

2. Patients must be receiving weekly paclitaxel or nab-paclitaxel chemotherapy or have recently completed paclitaxel or nab-paclitaxel chemotherapy and have at least a Grade I peripheral neuropathy (see Appendix A) because of therapy.

3. Because no dosing or adverse event data are currently available on the use of glutamine in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials.

4. ECOG performance status <1 (Karnofsky >90%).

5. Life expectancy of greater than 3 months.

6. Patients must have sufficient organ and marrow function so that paclitaxel treatment can be administered.

7. The effects of glutamine on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have experienced prior neuropathies not associated with chemotherapy

2. Patients may not be receiving any other investigational agents.

3. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4. There are no known allergies associated with glutamine.

5. Uncontrolled intercurrent illness that render the patient ineligible to receive paclitaxel chemotherapy.

6. Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with glutamine. Breastfeeding should also be discontinued if the mother is treated with glutamine.

7. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with glutamine. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

8. Concurrent chemotherapy with another drug known to cause neuropathy (CDDP or CBDCA or oxaliplatin) are excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Medical College of Cornell University	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Principal Investigator: Linda Vahdat, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00195013
• Other Study ID Numbers: 0309006308
• First Posted: Sep 19, 2005
• Last Update Posted: Jun 6, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Breast Neoplasms; Peripheral Nervous System Diseases

Study Results

Participant Flow

Arm/Group Title	Glutamine	Placebo
Arm/Group Description	10 grams three times a day (orally) for four days and then stop glutamine: 10 grams three times a day (orally) for four days and then stop	10 grams three times a day (orally) for four days and then stop Placebo: 10 grams three times a day (orally) for four days and then stop
Period Title: Overall Study
STARTED	14	16
COMPLETED	12	15
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Glutamine	Placebo	Total
Arm/Group Description	10 grams three times a day (orally) for four days and then stop glutamine: 10 grams three times a day (orally) for four days and then stop	10 grams three times a day (orally) for four days and then stop Placebo: 10 grams three times a day (orally) for four days and then stop	Total of all reporting groups
Overall Participants	14	16	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 78.6%	14 87.5%	25 83.3%
>=65 years	3 21.4%	2 12.5%	5 16.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	55	58
Sex: Female, Male (Count of Participants)
Female	14 100%	16 100%	30 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	16 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Change in Peripheral Neuropathy Score
Description	Used the clinical total neuropathy score scale (TNSc). The presence of sensory, motor, pin sensibility, vibration sensibility, DTR, autonomic symptoms was assessed. For each item, the possible score ranged between 0 (normal) and 4 (worst possible result). Outcomes calculated as neuropathy score value at 10 Weeks minus neuropathy score value at Baseline. Increased score value indicates increased neuropathy severity.
Time Frame	Duration of study, approximately 10 weeks per subject

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glutamine	Placebo
Arm/Group Description	10 grams three times a day (orally) for four days and then stop glutamine: 10 grams three times a day (orally) for four days and then stop	10 grams three times a day (orally) for four days and then stop Placebo: 10 grams three times a day (orally) for four days and then stop
Measure Participants	14	16
Mean (Full Range) [Change in Total Neuropathy Score]	0.3	0.9

Adverse Events

Arm/Group Title	Glutamine		Placebo
Arm/Group Description	10 grams three times a day (orally) for four days and then stop glutamine: 10 grams three times a day (orally) for four days and then stop		10 grams three times a day (orally) for four days and then stop Placebo: 10 grams three times a day (orally) for four days and then stop
All Cause Mortality
	Glutamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Glutamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Glutamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.