Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, Stage II, or Stage IIIA Breast Cancer Undergoing Chemotherapy - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00775645

Purpose

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.

Condition	Intervention	Phase
Breast Cancer Chemotherapeutic Agent Toxicity Fatigue Neuropathy Neurotoxicity	Dietary Supplement: acetyl-L-carnitine hydrochloride Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind Primary Purpose: Supportive Care
Official Title:	Randomized Placebo-Controlled Trial of Acetyl-L-Carnitine (ALC) for the Prevention of Taxane Induced Neuropathy Phase III

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer Charcot-Marie-Tooth disease hereditary neuropathy with liability to pressure palsies

MedlinePlus related topics: Breast Cancer Cancer Fatigue

Drug Information available for: Carnitine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Neurotoxicity as measured by the 11-item neurotoxicity component of the FACT-Taxane Questionnaire at baseline and at 12 weeks [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Functional status as measured by the FACT-Taxane Trial Outcome Index at baseline and at 12, 24, and 36 weeks [ Designated as safety issue: No ]
Fatigue as measured by the FACIT-Fatigue Symptom Module at baseline and at 12, 24, and 36 weeks [ Designated as safety issue: No ]
Proportion of patients experiencing grade 2 or 3 neuropathy as measured by NCI CTCAE v3.0 criteria at 12, 24, and 36 weeks [ Designated as safety issue: Yes ]
Nerve growth factor levels at baseline and 12 weeks [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
Relationship between nerve growth factor levels and the degree of neuropathy and functional status [ Designated as safety issue: No ]
Relationship between genetic markers responsible for taxane metabolism and clearance and degree of neuropathy [ Designated as safety issue: No ]

Estimated Enrollment:	380
Study Start Date:	September 2009
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks.	Dietary Supplement: acetyl-L-carnitine hydrochloride Given orally
Placebo Comparator: Arm II Patients receive oral placebo 3 times daily for 24 weeks.	Other: placebo Given orally

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 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775645

Show 295 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Laurence H. Baker, DO, FACOI

University of Michigan Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00775645 History of Changes
Other Study ID Numbers:	CDR0000617081, SWOG-S0715
Study First Received:	October 17, 2008
Last Updated:	February 8, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Breast Neoplasms
Fatigue
Neurotoxicity Syndromes
Demyelinating Diseases
Polyneuropathies
Nerve Compression Syndromes
Neurologic Manifestations
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Nervous System Diseases
Poisoning

Substance-Related Disorders
Peripheral Nervous System Diseases
Neuromuscular Diseases
Acetylcarnitine
Carnitine
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012