Levocarnitine in Treating Fatigue in Cancer Patients

Fatigue Clinical Trial

Official title:

Phase III Randomized Placebo-Controlled Trial to Determine Efficacy of Levocarnitine for Fatigue in Patients With Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00091169
• Other study ID #: E4Z02
• Secondary ID: E4Z02U10CA023318
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2005
• Est. completion date: May 2011

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 376
• Est. completion date: May 2011
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fatigue
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Dietary Supplement:
• levocarnitine
Given orally

Other:
• placebo
Given orally

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cruciani RA, Zhang JJ, Manola J, Cella D, Ansari B, Fisch MJ. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin On — View Citation

Rich TA, Fisch MJ, Manola J, et al.: Analysis of cytokines in ECOG E4Z02: A phase III randomized study of l-carnitine supplementation for fatigue in patients with cancer. [Abstract] J Clin Oncol 27 (Suppl 15): A-9635, 2009.

Rich TA, Manola J, Cella D, et al.: An evaluation of serum cytokine levels and fatigue and depression in ECOG E4Z02. [Abstract] J Clin Oncol 29 (Suppl 15): A-9046, 2011.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Score Change in Fatigue Measured With Brief Fatigue Inventory From Baseline to 4 Weeks	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.	assessed at baseline and 4 weeks after randomization
Secondary	Mean Score Change in Fatigue Measured With FACIT-F From Baseline to 4 Weeks	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.	assessed at baseline and 4 weeks after randomization
Secondary	Mean Score Change in Depression Measured With CES-D Between 4 Weeks and Baseline	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.	assessed at baseline and 4 weeks after randomization
Secondary	Mean Score Change in Pain Measured With Brief Pain Inventory From Baseline to 4 Weeks	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.	assessed at baseline and 4 weeks after randomization
Secondary	Prevalence of Carnitine Deficiency at 4 Weeks	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.	assessed at 4 weeks after randomization
Secondary	Proportion of Patients With Stable or Improving Performance Status at 4 Weeks	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.	assessed at baseline and 4 weeks after randomization