Levocarnitine in Treating Fatigue in Cancer Patients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Fatigue, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: levocarnitine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. | Dietary Supplement: levocarnitine<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo twice daily on weeks 1-4. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatigue, unspecified adult solid tumor, protocol specific, levocarnitine, depression, pain, carnitine deficiency