Trial Outcomes & Findings for S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo (NCT NCT00775645)

NCT ID: NCT00775645

Last Updated: 2017-08-14

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 437 participants
• Primary outcome timeframe: 12 weeks post-registration
• Results posted on: 2017-08-14

Participant Flow

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

Participant milestones

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) Patients receive oral placebo 3 times daily for 24 weeks
Overall Study STARTED	208	201
Overall Study COMPLETED	191	181
Overall Study NOT COMPLETED	17	20

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=208 Participants Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=201 Participants Patients receive oral placebo 3 times daily for 24 weeks	Total n=409 Participants Total of all reporting groups
Age, Continuous	52 years n=5 Participants	50 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	208 Participants n=5 Participants	201 Participants n=7 Participants	409 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=5 Participants	15 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	181 Participants n=5 Participants	177 Participants n=7 Participants	358 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) White	160 Participants n=5 Participants	165 Participants n=7 Participants	325 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Zubrod Performance Status 0	156 Participants n=5 Participants	146 Participants n=7 Participants	302 Participants n=5 Participants
Zubrod Performance Status 1	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Zubrod Performance Status 2	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Breast cancer stage I	57 Participants n=5 Participants	50 Participants n=7 Participants	107 Participants n=5 Participants
Breast cancer stage II	110 Participants n=5 Participants	107 Participants n=7 Participants	217 Participants n=5 Participants
Breast cancer stage III	41 Participants n=5 Participants	43 Participants n=7 Participants	84 Participants n=5 Participants
Breast cancer stage Not measurable/measured	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Taxane regiment Paclitaxel	124 Participants n=5 Participants	123 Participants n=7 Participants	247 Participants n=5 Participants
Taxane regiment Docetaxel	84 Participants n=5 Participants	77 Participants n=7 Participants	161 Participants n=5 Participants
Taxane regiment Not measurable/measured	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=191 Participants Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=181 Participants Patients receive oral placebo 3 times daily for 24 weeks
12-week FACT-Taxane Neurotoxicity Model-adjusted Score in ALC and Placebo Groups	35.4 units on a scale Interval 34.1 to 36.7	36.3 units on a scale Interval 35.0 to 37.6

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=191 Participants Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=181 Participants Patients receive oral placebo 3 times daily for 24 weeks
12-week FACT-Trial Outcome Index(TOI) Functional Status Model-adjusted Score in ALC and Placebo Groups	92.1 units on a scale Interval 89.3 to 94.9	92.3 units on a scale Interval 89.4 to 95.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=191 Participants Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=181 Participants Patients receive oral placebo 3 times daily for 24 weeks
12-week FACIT-fatigue Model-adjusted Score in ALC and Placebo Groups	36.6 FACIT-fatigue score Interval 34.7 to 38.6	35.3 FACIT-fatigue score Interval 33.4 to 37.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks post-registration

Proportion of patients experiencing grade 3 or 4 neuropathy

Outcome measures

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=202 Participants Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=194 Participants Patients receive oral placebo 3 times daily for 24 weeks
Proportion of Patients Experiencing Grade 3 or 4 Neuropathy	8 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks post-registration

Population: Data still in process; Analysis to be performed in future.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks post-registration

Population: Data still in process; Analysis to be performed in future.

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks post-registration

Population: Data still in process; Analysis to be performed in future.

Explore the relationship between nerve growth factor levels and the degree of neuropathy and functional status in these patients.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks post-registration

Population: Data still in process; Analysis to be performed in future.

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.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Acetyl-L-carnitine Hydrochloride))

Serious events: 1 serious events

Other events: 156 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 0 serious events

Other events: 153 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=208 participants at risk Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=201 participants at risk Patients receive oral placebo 3 times daily for 24 weeks
Investigations Neutrophils/granulocytes (ANC/AGC)	0.48% 1/208 • Up to 25 weeks	0.00% 0/201 • Up to 25 weeks

Other adverse events

Measure	Arm I (Acetyl-L-carnitine Hydrochloride)) n=208 participants at risk Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks	Arm II (Placebo) n=201 participants at risk Patients receive oral placebo 3 times daily for 24 weeks
Gastrointestinal disorders Diarrhea	6.2% 13/208 • Up to 25 weeks	5.0% 10/201 • Up to 25 weeks
Gastrointestinal disorders Nausea	22.1% 46/208 • Up to 25 weeks	25.4% 51/201 • Up to 25 weeks
Gastrointestinal disorders Vomiting	8.2% 17/208 • Up to 25 weeks	7.0% 14/201 • Up to 25 weeks
General disorders Fatigue (asthenia, lethargy, malaise)	18.3% 38/208 • Up to 25 weeks	15.9% 32/201 • Up to 25 weeks
Musculoskeletal and connective tissue disorders Pain - Joint	6.2% 13/208 • Up to 25 weeks	6.0% 12/201 • Up to 25 weeks
Nervous system disorders Extrapyramidal/involuntary movement/restlessness	5.8% 12/208 • Up to 25 weeks	4.5% 9/201 • Up to 25 weeks
Nervous system disorders Neuropathy: motor	8.7% 18/208 • Up to 25 weeks	8.0% 16/201 • Up to 25 weeks
Nervous system disorders Neuropathy: sensory	61.1% 127/208 • Up to 25 weeks	63.2% 127/201 • Up to 25 weeks
Psychiatric disorders Insomnia	24.5% 51/208 • Up to 25 weeks	22.4% 45/201 • Up to 25 weeks
Vascular disorders Hot flashes/flushes	10.1% 21/208 • Up to 25 weeks	7.0% 14/201 • Up to 25 weeks

Additional Information

Study Statistician

SWOG Statistical Center

Phone: 206-667-4623

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place