Levocarnitine in Treating Fatigue in Cancer Patients

ECOG-ACRIN Cancer Research Group

Status and phase: Completed; Phase 3

Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Fatigue

Treatments: Dietary Supplement: levocarnitine; Other: placebo

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00091169

E4Z02 (Other Identifier)

U10CA023318 (U.S. NIH Grant/Contract)

CDR0000384087 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 376 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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376 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4.

Treatment:

Dietary Supplement: levocarnitine

Arm II

Placebo Comparator group

Description:

Patients receive oral placebo twice daily on weeks 1-4.

Treatment:

Other: placebo