Levocarnitine in Treating Fatigue in Cancer Patients

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT00091169
First received: September 7, 2004
Last updated: May 3, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Fatigue
Unspecified Adult Solid Tumor, Protocol Specific
Dietary Supplement: levocarnitine
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Phase III Randomized Placebo-Controlled Trial to Determine Efficacy of Levocarnitine for Fatigue in Patients With Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Mean Score Change in Fatigue Measured With Brief Fatigue Inventory From Baseline to 4 Weeks [ Time Frame: assessed at baseline and 4 weeks after randomization ] [ Designated as safety issue: No ]
    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:
  • Mean Score Change in Fatigue Measured With FACIT-F From Baseline to 4 Weeks [ Time Frame: assessed at baseline and 4 weeks after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: assessed at baseline and 4 weeks after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: assessed at baseline and 4 weeks after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: assessed at 4 weeks after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: assessed at baseline and 4 weeks after randomization ] [ Designated as safety issue: No ]
    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.


Enrollment: 376
Study Start Date: November 2005
Study Completion Date: May 2011
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4.
Dietary Supplement: levocarnitine
Given orally
Placebo Comparator: Arm II
Patients receive oral placebo twice daily on weeks 1-4.
Other: placebo
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091169

  Show 116 Study Locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Study Chair: Ricardo Cruciani, MD, PhD Beth Israel Medical Center - Petrie Division
Study Chair: Russell K. Portenoy, MD Beth Israel Medical Center - Petrie Division
  More Information

Publications:
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.
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.

Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT00091169     History of Changes
Other Study ID Numbers: E4Z02  E4Z02  U10CA023318  CDR0000384087 
Study First Received: September 7, 2004
Results First Received: February 2, 2016
Last Updated: May 3, 2016
Health Authority: United States: Federal Government
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Keywords provided by Eastern Cooperative Oncology Group:
fatigue
unspecified adult solid tumor, protocol specific
levocarnitine
depression
pain
carnitine deficiency

Additional relevant MeSH terms:
Fatigue
Signs and Symptoms

ClinicalTrials.gov processed this record on August 29, 2016