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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00775645
First Posted: October 20, 2008
Last Update Posted: August 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: S0715: Randomized Placebo-Controlled Trial of Acetyl-L-Carnitine (ALC) for the Prevention of Taxane Induced Neuropathy Phase III

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 12-week FACT-Taxane Neurotoxicity Model-adjusted Score in ALC and Placebo Groups [ Time Frame: 12 weeks post-registration ]
    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


Secondary Outcome Measures:
  • 12-week FACT-Trial Outcome Index(TOI) Functional Status Model-adjusted Score in ALC and Placebo Groups [ Time Frame: 12 weeks post-registration ]
    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-week FACIT-fatigue Model-adjusted Score in ALC and Placebo Groups [ Time Frame: 12 weeks post-registration ]
    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


Other Outcome Measures:
  • Proportion of Patients Experiencing Grade 3 or 4 Neuropathy [ Time Frame: 12 weeks post-registration ]
    Proportion of patients experiencing grade 3 or 4 neuropathy

  • Serum Nerve Growth Factor Levels [ Time Frame: 12 weeks post-registration ]
  • Treatment and Concurrent Therapy [ Time Frame: 12 weeks post-registration ]
    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

  • Association Between Nerve Growth Factor Levels and the Degree of Neuropathy and Functional Status [ Time Frame: 12 weeks post-registration ]
    Explore the relationship between nerve growth factor levels and the degree of neuropathy and functional status in these patients.

  • Association Between Genetic Markers Responsible for Taxane Metabolism and Clearance and the Degree of Neuropathy [ Time Frame: 12 weeks post-registration ]
    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.


Enrollment: 437
Study Start Date: September 2009
Study Completion Date: June 2013
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 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications:
Hershman DL, Unger JM, Crew KD, et al.: SWOG S0715: randomized placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy during adjuvant breast cancer therapy. [Abstract] J Clin Oncol 30 (Suppl 15): A-9018, 2012.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00775645     History of Changes
Other Study ID Numbers: CDR0000617081
S0715 ( Other Identifier: SWOG )
U10CA037429 ( U.S. NIH Grant/Contract )
First Submitted: October 17, 2008
First Posted: October 20, 2008
Results First Submitted: November 14, 2016
Results First Posted: April 10, 2017
Last Update Posted: August 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Southwest Oncology Group:
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:
Neurotoxicity Syndromes
Breast Neoplasms
Fatigue
Peripheral Nervous System Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Neuromuscular Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Acetylcarnitine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Nootropic Agents