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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00775645

Enrollment

437

Registered

2008-10-20

Start date

2009-09-30

Completion date

2013-06-30

Last updated

2017-08-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer, Chemotherapeutic Agent Toxicity, Fatigue, Neuropathy, Neurotoxicity

Keywords

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

Brief summary

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.

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.

Interventions

DIETARY_SUPPLEMENTacetyl-L-carnitine hydrochloride

Given orally

OTHERplacebo

Given orally

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 120 Years

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
12-week FACT-Taxane Neurotoxicity Model-adjusted Score in ALC and Placebo Groups	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

Measure	Time frame	Description
12-week FACT-Trial Outcome Index(TOI) Functional Status Model-adjusted Score in ALC and Placebo Groups	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	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

Measure	Time frame	Description
Association Between Nerve Growth Factor Levels and the Degree of Neuropathy and Functional Status	12 weeks post-registration	Explore the relationship between nerve growth factor levels and the degree of neuropathy and functional status in these patients.
Proportion of Patients Experiencing Grade 3 or 4 Neuropathy	12 weeks post-registration	Proportion of patients experiencing grade 3 or 4 neuropathy
Association Between Genetic Markers Responsible for Taxane Metabolism and Clearance and the Degree of Neuropathy	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.
Serum Nerve Growth Factor Levels	12 weeks post-registration	—
Treatment and Concurrent Therapy	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

Countries

United States

Participant flow

Pre-assignment details

Of the 437 accrued patients, 27 were ineligible and 1 withdrew consent.

Participants by arm

Arm	Count
Arm I (Acetyl-L-carnitine Hydrochloride)) Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	208
Arm II (Placebo) Patients receive oral placebo 3 times daily for 24 weeks	201
Total	409

Baseline characteristics

Characteristic	Total	Arm I (Acetyl-L-carnitine Hydrochloride))	Arm II (Placebo)
Age, Continuous	52 years	52 years	50 years
Breast cancer stage I	107 Participants	57 Participants	50 Participants
Breast cancer stage II	217 Participants	110 Participants	107 Participants
Breast cancer stage III	84 Participants	41 Participants	43 Participants
Breast cancer stage Not measurable/measured	1 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants	21 Participants	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	358 Participants	181 Participants	177 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants	6 Participants	9 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	20 Participants	12 Participants	8 Participants
Race (NIH/OMB) Black or African American	37 Participants	17 Participants	20 Participants
Race (NIH/OMB) More than one race	3 Participants	2 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants	4 Participants	2 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants	12 Participants	5 Participants
Race (NIH/OMB) White	325 Participants	160 Participants	165 Participants
Sex: Female, Male Female	409 Participants	208 Participants	201 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
Taxane regiment Docetaxel	161 Participants	84 Participants	77 Participants
Taxane regiment Not measurable/measured	1 Participants	0 Participants	1 Participants
Taxane regiment Paclitaxel	247 Participants	124 Participants	123 Participants
Zubrod Performance Status 0	302 Participants	156 Participants	146 Participants
Zubrod Performance Status 1	105 Participants	51 Participants	54 Participants
Zubrod Performance Status 2	2 Participants	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	156 / 208	153 / 201
serious Total, serious adverse events	1 / 208	0 / 201

Outcome results

Primary

12-week FACT-Taxane Neurotoxicity Model-adjusted Score in ALC and Placebo Groups

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