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

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Chemotherapeutic Agent Toxicity; Breast Cancer; Neuropathy; Fatigue; Neurotoxicity

Treatments: Dietary Supplement: acetyl-L-carnitine hydrochloride; Other: placebo

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00775645

S0715 (Other Identifier)

CDR0000617081

U10CA037429 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 437 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

437 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks.

Treatment:

Dietary Supplement: acetyl-L-carnitine hydrochloride

Arm II

Placebo Comparator group

Description:

Patients receive oral placebo 3 times daily for 24 weeks.

Treatment:

Other: placebo