Levocarnitine in Treating Fatigue in Cancer Patients

Phase 3

Completed

Conditions: Fatigue
Unspecified Adult Solid Tumor, Protocol Specific

Interventions: Other: placebo
Dietary Supplement: levocarnitine

Registration Number: NCT00091169

Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary: RATIONALE: Levocarnitine may help improve energy levels in cancer patients.

PURPOSE: This randomized phase III trial is studying how well levocarnitine works compared to a placebo in treating fatigue in cancer patients.

Detailed Description: OBJECTIVES:

Primary Objective:

* Compare the efficacy of levocarnitine (L-carnitine) supplementation vs placebo for the management of fatigue in patients with cancer.

Secondary Objectives:

* Assess the effect of levocarnitine on pain, depression and performance status at 4 and 8 weeks of follow-up.

* Determine the prevalence of serum carnitine deficiency in patients treated with these regimens.

* Explore the association between carnitine deficiency and fatigue.

* Present the toxicity profiles of all patients.

Correlative Objective:

* Measure serum levels of the pro-inflammatory cytokines and growth factors and correlate with fatigue and other onco-behavioral symptoms.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, ECOG performance status (0-1 vs 2-3), and concurrent chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.

* Arm I (levocarnitine): Patients receive oral levocarnitine (L-carnitine) twice daily (2000 mg/day) on weeks 1-4.

* Arm II (placebo): Patients receive oral placebo twice daily (2000 mg/day) on weeks 1-4.

The dose was titrated over a 2-day period (i.e. two 500 mg doses the first day and two 1000 mg doses the second day) to avoid gastrointestinal side effects. Patients then continued to receive two daily doses of 1000 mg on days 3 to 28.

After week 4, all patients (on both arms) receive open-label oral L-carnitine twice daily on weeks 5-8 (extension phase) administered in the same fashion as during the first 4 weeks. For patients who had received a dose modification during weeks 1 to 4, they received the same reduced dose during the extension phase (without titration)

Fatigue, pain, and depression are assessed at baseline and then at weeks 4 and 8.

PROJECTED ACCRUAL: A total of 352 patients will be accrued for this study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 376

Inclusion Criteria

Diagnosis of an invasive malignant disorder
Moderate to severe fatigue within the past 4 weeks, defined as a score of ≥ 2 (on a scale of 0-4) on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) question "I feel fatigued"
Age 18 and over
Eastern Cooperative Oncology Group (ECOG) Performance status of 0-3
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation

Exclusion Criteria

Brain metastases
Hemoglobin < 9 g/dL, taken <=4 weeks prior to registration
Severe, uncontrolled liver disease
Evidence of severely compromised renal function including any 1 of the following:
- Renal failure
- End stage renal disease
- Ongoing renal dialysis
Severe, uncontrolled cardiovascular disease
Severe, uncontrolled pulmonary disease
Pregnant or nursing
History of seizures
Known sensitivity to carnitine
Delirium
Nausea > grade 1
Taking any form of levocarnitine (L-carnitine) supplementation or nutritional supplements containing carnitine within 2 months prior to registration

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II	placebo	Patients receive oral placebo twice daily on weeks 1-4.
Arm I	levocarnitine	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4.

Primary Outcome Measures

Name	Time	Method
Mean Score Change in Fatigue Measured With Brief Fatigue Inventory From Baseline to 4 Weeks	assessed at baseline and 4 weeks after randomization	Fatigue was measured using Brief Fatigue Inventory (BFI). The average of all 9 items included in the scale (range: 0-10) was used to measure fatigue level, and a higher average represented worse fatigue. Score change= BFI score at 4 weeks - BFI score at baseline.

Secondary Outcome Measures

Name	Time	Method
Mean Score Change in Fatigue Measured With FACIT-F From Baseline to 4 Weeks	assessed at baseline and 4 weeks after randomization	Fatigue was measured using Functional Assessment of Cancer Therapy- Fatigue subscale (FACIT-F). The sum of the scores for all 13 items (range: 0-52) included in the scale was used to measure fatigue level, and lower score represented worse fatigue. Score change= FACIT-F score at 4 weeks - FACIT-F score at baseline.
Mean Score Change in Depression Measured With CES-D Between 4 Weeks and Baseline	assessed at baseline and 4 weeks after randomization	Depression was measured using Center for Epidemiologic Studies Depression Scale (CES-D). The sum of the scores for all 20 items (range: 0-60) was used to assess depression level, and higher scores indicated a higher level of depression. Score change= CES-D score at 4 weeks - CES-D score at baseline.
Mean Score Change in Pain Measured With Brief Pain Inventory From Baseline to 4 Weeks	assessed at baseline and 4 weeks after randomization	Pain was measured using Brief Pain Inventory (BPI). The mean of the 4 severity items (range: 0-10 with 0 representing no pain and 10 representing pain as bad as you can imagine) was used to measure pain severity. Score change= BPI score at 4 weeks - BPI score at baseline.
Prevalence of Carnitine Deficiency at 4 Weeks	assessed at 4 weeks after randomization	Carnitine deficiency is defined as a ratio of acylcarnitine (total-free) to free carnitine \> 0.4 μmol/L or free carnitine \< 35 μmol/L for males and \< 25 μmol/L for females.
Proportion of Patients With Stable or Improving Performance Status at 4 Weeks	assessed at baseline and 4 weeks after randomization	Performance status (PS) was measured using Eastern Cooperative Oncology Group performance status scale. Lower score represents better PS. Change in PS was calculated by PS at week 4- PS at baseline. Patients with negative value for change in PS were considered to have stable or improving PS.

Trial Locations

Locations (116): Licking Memorial Cancer Care Program at Licking Memorial Hospital
🇺🇸
Newark, Ohio, United States
Bay Area Cancer Care Center at Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Eureka Community Hospital
🇺🇸
Eureka, Illinois, United States
Community Cancer Center
🇺🇸
Normal, Illinois, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸
Urbana, Illinois, United States
Mercy Medical Center
🇺🇸
Springfield, Ohio, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Albert Einstein Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Geisinger Medical Group - Scenery Park
🇺🇸
State College, Pennsylvania, United States
York Cancer Center at Apple Hill Medical Center
🇺🇸
York, Pennsylvania, United States
Jennersville Regional Hospital
🇺🇸
West Grove, Pennsylvania, United States
Praxair Cancer Center at Danbury Hospital
🇺🇸
Danbury, Connecticut, United States
Veterans Affairs Medical Center - Palo Alto
🇺🇸
Palo Alto, California, United States
Stanford Comprehensive Cancer Center - Stanford
🇺🇸
Stanford, California, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
Graham Hospital
🇺🇸
Canton, Illinois, United States
Baptist Cancer Institute - Jacksonville
🇺🇸
Jacksonville, Florida, United States
St. Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Evanston Northwestern Healthcare - Evanston Hospital
🇺🇸
Evanston, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Galesburg Clinic, PC
🇺🇸
Galesburg, Illinois, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸
Joliet, Illinois, United States
Hopedale Medical Complex
🇺🇸
Hopedale, Illinois, United States
BroMenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
McDonough District Hospital
🇺🇸
Macomb, Illinois, United States
Community Hospital of Ottawa
🇺🇸
Ottawa, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸
Ottawa, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸
Peoria, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸
Pekin, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸
Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
OSF St. Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Illinois Valley Community Hospital
🇺🇸
Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
St. Margaret's Hospital
🇺🇸
Spring Valley, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Howard Community Hospital
🇺🇸
Kokomo, Indiana, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸
La Porte, Indiana, United States
Saint Anthony Memorial Health Centers
🇺🇸
Michigan City, Indiana, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
CCOP - Northern Indiana CR Consortium
🇺🇸
South Bend, Indiana, United States
Saint Joseph Regional Medical Center
🇺🇸
South Bend, Indiana, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸
Sioux City, Iowa, United States
McCreery Cancer Center at Ottumwa Regional
🇺🇸
Ottumwa, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸
Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
Green Bay Oncology, Limited - Escanaba
🇺🇸
Escanaba, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸
Grosse Pointe Woods, Michigan, United States
Dickinson County Healthcare System
🇺🇸
Iron Mountain, Michigan, United States
Foote Hospital
🇺🇸
Jackson, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Sparrow Regional Cancer Center
🇺🇸
Lansing, Michigan, United States
Seton Cancer Institute - Saginaw
🇺🇸
Saginaw, Michigan, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸
Saint Joseph, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸
Robbinsdale, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸
Saint Louis Park, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸
Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Veterans Affairs Medical Center - East Orange
🇺🇸
East Orange, New Jersey, United States
Veterans Affairs Medical Center - Brooklyn
🇺🇸
Brooklyn, New York, United States
Beth Israel Medical Center - Petrie Division
🇺🇸
New York, New York, United States
Riverside Methodist Hospital Cancer Care
🇺🇸
Columbus, Ohio, United States
Mercy Cancer Center at Mercy Medical Center
🇺🇸
Canton, Ohio, United States
Adena Regional Medical Center
🇺🇸
Chillicothe, Ohio, United States
CCOP - Columbus
🇺🇸
Columbus, Ohio, United States
Grant Medical Center Cancer Care
🇺🇸
Columbus, Ohio, United States
Mount Carmel Health - West Hospital
🇺🇸
Columbus, Ohio, United States
Grady Memorial Hospital
🇺🇸
Delaware, Ohio, United States
Doctors Hospital at Ohio Health
🇺🇸
Columbus, Ohio, United States
Strecker Cancer Center at Marietta Memorial Hospital
🇺🇸
Marietta, Ohio, United States
Fairfield Medical Center
🇺🇸
Lancaster, Ohio, United States
Community Hospital of Springfield and Clark County
🇺🇸
Springfield, Ohio, United States
Mount Carmel St. Ann's Cancer Center
🇺🇸
Westerville, Ohio, United States
Genesis - Good Samaritan Hospital
🇺🇸
Zanesville, Ohio, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
🇺🇸
Tulsa, Oklahoma, United States
Bryn Mawr Hospital
🇺🇸
Bryn Mawr, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Lewistown Hospital
🇺🇸
Lewistown, Pennsylvania, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸
Paoli, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸
State College, Pennsylvania, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
🇺🇸
Wilkes-Barre, Pennsylvania, United States
CCOP - MainLine Health
🇺🇸
Wynnewood, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸
Wynnewood, Pennsylvania, United States
Green Bay Oncology, Limited at St. Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Marshfield Clinic - Marshfield Center
🇺🇸
Marshfield, Wisconsin, United States
Green Bay Oncology, Limited - Oconto Falls
🇺🇸
Oconto Falls, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸
Rice Lake, Wisconsin, United States
Saint Joseph Mercy Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸
Ann Arbor, Michigan, United States
St. Mary's Hospital Medical Center - Green Bay
🇺🇸
Green Bay, Wisconsin, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸
Green Bay, Wisconsin, United States
St. John Macomb Hospital
🇺🇸
Warren, Michigan, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
Green Bay Oncology, Limited - Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Manchester Memorial Hospital
🇺🇸
Manchester, Connecticut, United States
Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
🇺🇸
Boca Raton, Florida, United States
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
🇺🇸
Green Bay, Wisconsin, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸
Madison, Wisconsin, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸
Bronx, New York, United States
Dean Medical Center - Madison
🇺🇸
Madison, Wisconsin, United States
St. Rita's Medical Center
🇺🇸
Lima, Ohio, United States