Trial Information

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

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
FACT-Taxane Questionnaire.

- Compare fatigue in these patients using the FACIT-Fatigue Symptom Module.

- Compare the proportion of patients experiencing grade 2 or 3 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.