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

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.