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

Study Overview
=================
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.

Detailed Description
-----------------
Determine whether oral glutamine supplementation can reduce the symptoms and signs of peripheral neuropathy. 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. Assess whether oral glutamine affects circulating nerve growth factor or insulin-like growth factor levels. Assess whether glutamine interferes with paclitaxel pharmacokinetics

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

Conditions
-----------------
Peripheral Neuropathy, Breast Cancer

Intervention / Treatment
-----------------
* Drug: glutamine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically or cytologically confirmed breast cancer, Stage I, II, III or IV or other solid tumors. 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. 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. ECOG performance status <1 (Karnofsky >90%). Life expectancy of greater than 3 months. Patients must have sufficient organ and marrow function so that paclitaxel treatment can be administered. 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. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have experienced prior neuropathies not associated with chemotherapy Patients may not be receiving any other investigational agents. 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. There are no known allergies associated with glutamine. Uncontrolled intercurrent illness that render the patient ineligible to receive paclitaxel chemotherapy. 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. 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. Concurrent chemotherapy with another drug known to cause neuropathy (CDDP or CBDCA or oxaliplatin) are excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glutamine<br>10 grams three times a day (orally) for four days and then stop | Drug: glutamine<br>* 10 grams three times a day (orally) for four days and then stop<br>* Other names: NutreStore;|
| Placebo Comparator: Placebo<br>10 grams three times a day (orally) for four days and then stop | Drug: Placebo<br>* 10 grams three times a day (orally) for four days and then stop<br>* Other names: sugar pill;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peripheral Neuropathy Score | 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. | Duration of study, approximately 10 weeks per subject |