S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
Condition: Breast Cancer; Chemotherapeutic Agent Toxicity; Fatigue; Neuropathy; Neurotoxicity
MeSH terms: Breast Neoplasms; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Fatigue
Study type: Interventional
Phase: Phase 3

Summary: 
      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: 
      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.
    

Intervention name(s): acetyl-L-carnitine hydrochloride; placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Given orally; Given orally
Intervention MeSH terms: Acetylcarnitine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: 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