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

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ClinicalTrials.gov Identifier: NCT00775645
Recruitment Status : Completed
First Posted : October 20, 2008
Results First Posted : April 10, 2017
Last Update Posted : August 14, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

October 17, 2008
October 20, 2008
November 14, 2016
April 10, 2017
August 14, 2017
September 2009
January 2012   (Final data collection date for primary outcome measure)
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
Neurotoxicity as measured by the 11-item neurotoxicity component of the FACT-Taxane Questionnaire at baseline and at 12 weeks
Complete list of historical versions of study NCT00775645 on ClinicalTrials.gov Archive Site
  • 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
  • Functional status as measured by the FACT-Taxane Trial Outcome Index at baseline and at 12, 24, and 36 weeks
  • Fatigue as measured by the FACIT-Fatigue Symptom Module at baseline and at 12, 24, and 36 weeks
  • Proportion of patients experiencing grade 2 or 3 neuropathy as measured by NCI CTCAE v3.0 criteria at 12, 24, and 36 weeks
  • Nerve growth factor levels at baseline and 12 weeks
  • 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 (CAM)
  • Relationship between nerve growth factor levels and the degree of neuropathy and functional status
  • Relationship between genetic markers responsible for taxane metabolism and clearance and degree of neuropathy
  • 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.
Not Provided
 
S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
S0715: Randomized Placebo-Controlled Trial of Acetyl-L-Carnitine (ALC) for the Prevention of Taxane Induced Neuropathy Phase III

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
  • Breast Cancer
  • Chemotherapeutic Agent Toxicity
  • Fatigue
  • Neuropathy
  • Neurotoxicity
  • Dietary Supplement: acetyl-L-carnitine hydrochloride
    Given orally
  • Other: placebo
    Given orally
  • Experimental: Arm I
    Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks.
    Intervention: Dietary Supplement: acetyl-L-carnitine hydrochloride
  • Placebo Comparator: Arm II
    Patients receive oral placebo 3 times daily for 24 weeks.
    Intervention: Other: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
437
June 2013
January 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Female
18 Years to 120 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00775645
CDR0000617081
S0715 ( Other Identifier: SWOG )
U10CA037429 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Laurence H. Baker, DO, FACOI University of Michigan Cancer Center
Southwest Oncology Group
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP