S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo

Study Overview
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Brief Summary
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RATIONALE: Acetyl-L-carnitine may prevent or lessen neuropathy caused by chemotherapy. It is not yet known whether acetyl-L-carnitine is more effective than a placebo in preventing neuropathy caused by chemotherapy. PURPOSE: This randomized phase III trial is studying acetyl-L-carnitine to see how well it works compared with a placebo in preventing neuropathy in women with stage I, stage II, or stage III breast cancer undergoing chemotherapy.

Detailed Description
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OBJECTIVES: Primary Compare whether treatment with acetyl-L-carnitine hydrochloride vs placebo prevents symptoms of neuropathy as measured by the 11-item neurotoxicity component of the FACT-Taxane Questionnaire at 12 weeks after study registration in women with stage I, II, or IIIA breast cancer undergoing adjuvant taxane-based chemotherapy. Secondary Compare the functional status of these patients using the Trial Outcome Index from the Functional Assessment of Cancer Therapy (FACT)-Taxane Questionnaire. Compare fatigue in these patients using the Function Assessment of Chronic Illness Therapy (FACIT)-Fatigue Symptom Module. Other Compare the proportion of patients experiencing grade 3 or 4 neuropathy. Compare serum nerve growth factor levels in these patients. Describe the total dose of taxane received and treatment delays, compliance with therapy, and use of concurrent medications, dietary supplements (e.g., glutamine), vitamin E, and complementary and alternative medicines in these patients. Explore the relationship between nerve growth factor levels and the degree of neuropathy and functional status in these patients. Explore the relationship between genetic markers responsible for taxane metabolism and clearance (e.g., CYP2C8, CYP3A4, CYP3A5, GSTM1, and GSTP1) and the degree of neuropathy in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to planned adjuvant chemotherapy regimen for breast cancer (paclitaxel weekly for 12 weeks vs paclitaxel biweekly for 4 courses [8 weeks] vs paclitaxel biweekly for 6 courses [12 weeks] vs docetaxel every 3 weeks for 4 courses [12 weeks] vs docetaxel every 3 weeks for 6 courses [18 weeks]) and age (< 60 years vs ≥ 60 years). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks. Arm II: Patients receive oral placebo 3 times daily for 24 weeks. Patients complete the FACT-Taxane Trial Outcome Index and the FACIT-Fatigue Symptom Module questionnaires at baseline, at 12, 24, and 36 weeks, and at 1 and 2 years. Blood samples are collected at baseline and at week 12 for biomarker analysis (nerve growth factor levels) by ELISA, DNA extraction, and genotyping analysis.

Official Title
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S0715: Randomized Placebo-Controlled Trial of Acetyl-L-Carnitine (ALC) for the Prevention of Taxane Induced Neuropathy Phase III

Conditions
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Breast Cancer, Chemotherapeutic Agent Toxicity, Fatigue, Neuropathy, Neurotoxicity

Intervention / Treatment
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* Dietary Supplement: acetyl-L-carnitine hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary invasive adenocarcinoma of the breast Stage I-III disease No metastatic disease Must have undergone modified radical mastectomy or breast-sparing surgery Planning to receive one of the following standard taxane-based systemic chemotherapy regimens as adjuvant therapy for breast cancer: Paclitaxel 80 mg/m² weekly for 12 weeks Paclitaxel 175 mg/m² every other week for 4 courses (8 weeks) Paclitaxel 175 mg/m² every other week for 6 courses (12 weeks) Docetaxel 75 mg/m² every 3 weeks for 4 courses (12 weeks) Docetaxel 75 mg/m² every 3 weeks for 6 courses (18 weeks) No history of neuropathy Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Zubrod performance status 0-2 Serum creatinine ≤ 2.5 times upper limit of normal Not pregnant or nursing Fertile patients must use effective contraception Able to complete questionnaires in English or Spanish Willing to submit blood samples for DNA extraction, genotyping analysis, and nerve growth factor studies No history of diabetes No history of seizure disorder No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal carcinoma in situ, or adequately treated stage I or stage II malignancy from which the patient is currently in complete remission PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior breast surgery Prior neoadjuvant or adjuvant chemotherapy allowed No prior taxane therapy No prior biologic therapy for treatment of breast cancer No concurrent vitamin E, glutamine, gabapentin, nortriptyline, amitriptyline, or duloxetine hydrochloride Multivitamins containing vitamin E allowed provided vitamin E dose is < 1,000 IU No concurrent anti-seizure medications Concurrent hormonal therapy allowed Concurrent biologic therapy allowed (e.g., Herceptin) Concurrent participation in another therapeutic clinical trial allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks. | Dietary Supplement: acetyl-L-carnitine hydrochloride<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo 3 times daily for 24 weeks. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-week FACT-Taxane Neurotoxicity Model-adjusted Score in ALC and Placebo Groups | Compare whether treatment with acetyl-L-carnitine hydrochloride vs placebo prevents symptoms of neuropathy as measured by the 11-item neurotoxicity (NTX) component of the Functional Assesment of Cancer Therapy (FACT)-Taxane Questionnaire at 12 weeks after study registration in women with breast cancer undergoing adjuvant taxane-based chemotherapy. Linear regression model adjusted for baseline score, taxane regiment, and age. Lower scores indicate worse CIPN. Total possible range is 0 to 64. For more information on this subscale, please see http://www.facit.org/FACITOrg/Questionnaires | 12 weeks post-registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-week FACT-Trial Outcome Index(TOI) Functional Status Model-adjusted Score in ALC and Placebo Groups | Compare FACT-TOI outcome in treatment vs placebo groups at 12 weeks after study registration in women with breast cancer undergoing adjuvant taxane-based chemotherapy. Linear regression model adjusted for baseline score, taxane regiment, and age. Lower scores indicate worse functional status. Total possible range is 0 to 120. For more information on this subscale, please see http://www.facit.org/FACITOrg/Questionnaires | 12 weeks post-registration | 
| 12-week FACIT-fatigue Model-adjusted Score in ALC and Placebo Groups | Compare fatigue outcome between treatment and placebo groups as measured by the 13-item Functional Assessment of Chronic Illness Therapy FACIT-fatigue questionnaire at 12 weeks after study registration in women with breast cancer undergoing adjuvant taxane-based chemotherapy. Linear regression model adjusted for baseline score, taxane regiment, and age. Lower scores indicate more fatigue. Total possible range is 0 to 52. For more information on this subscale, please see http://www.facit.org/FACITOrg/Questionnaires | 12 weeks post-registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurotoxicity, chemotherapeutic agent toxicity, fatigue, neuropathy, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer