Physical Activity and Dexamethasone in Reducing Cancer-Related Fatigue in Patients With Advanced Cancer

Phase 2

Active, not recruiting

Conditions: Recurrent Malignant Neoplasm
Advanced Malignant Neoplasm
Refractory Malignant Neoplasm
Fatigue
Metastatic Malignant Neoplasm

Interventions: Drug: Dexamethasone
Behavioral: Exercise Intervention
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT02491632

Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary: This randomized phase II trial studies how well physical activity and dexamethasone work in reducing cancer-related fatigue in patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Dexamethasone is approved for the treatment of tiredness, pain, and nausea. Physical activity may help improve cancer-related fatigue by improvement in symptoms, distress, and overall well-being. It is not yet known whether high dose or low dose dexamethasone combined with physical activity works better in reducing fatigue in patients with advanced cancer.

Detailed Description: PRIMARY OBJECTIVES:

1. To determine the feasibility, adherence, and satisfaction with physical activity (PA) plus dexamethasone (PA+ DEX).

SECONDARY OBJECTIVES:

I. To explore the preliminary efficacy of PA+ Hi Dex group (PA for 4 weeks plus high dose dexamethasone for 1 week) and PA + Lo Dex groups (PA for 4 weeks plus low dose dexamethasone for 1 week) on cancer-related fatigue (CRF) as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at the end of one week.

II. To explore the effects of PA+ Hi Dex on the various dimensions of CRF (Patient-Reported Outcomes Measurement Information System-Fatigue \[PROMIS-F\]), i.e., affective/emotional (Hospital Anxiety Depression Scale \[HADS\]); physical/behavioral (the Multidimensional Fatigue Symptom Inventory-Short Form \[MFSI-SF\], Pittsburg Sleep Quality Index), physical activity and function (30 second sit-to stand test, six minute walk test) before and after treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive high-dose dexamethasone orally (PO) twice daily (BID) for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.

ARM II: Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.

After completion of study, patients are followed up at day 29 and again after 1 month.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 90

Inclusion Criteria

A diagnosis of advanced cancer (defined as metastatic or recurrent) with fatigue >= 4/10 (0-10 scale) on the Edmonton Symptom Assessment Scale (ESAS)
The presence of fatigue for at least 2 weeks
Normal cognition
Hemoglobin > 8 g/L within 1 week of enrollment in the study
A life expectancy of >= 4 months
No evidence of significant anxiety or depression as determined by a total HADS scores of < 21
Definition of advanced cancer includes those patients who have metastatic or refractory disease according to their treating oncologist
Patients must be able to understand, read, write, and speak English or Spanish

Exclusion Criteria

Patients with a history of hypersensitivity to dexamethasone or having any contraindication to physical activity as determined by the treating physician
Reports a fall in the past 30 days
Uncontrolled diabetes mellitus as defined by a random blood sugar of > 200 mg/dl not being monitored by their primary care physician
Sepsis and/or acute, chronic, or ongoing infections that are currently being treated with systemic antimicrobials
Will exclude patients with current, active peptic ulcer disease
Neutropenia as defined by an absolute neutrophil count (ANC) of < 1000 cells/mm
Regular participation in moderate- or vigorous-intensity physical activity for >= 30 minutes at least 5 times a week and strength training for >= 2 days
Severe cardiac disease (New York Heart Association functional class III or IV) or coronary artery disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (high-dose dexamethasone, physical activity)	Laboratory Biomarker Analysis	Patients receive high-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm I (high-dose dexamethasone, physical activity)	Questionnaire Administration	Patients receive high-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm II (low dose dexamethasone, physical activity)	Laboratory Biomarker Analysis	Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm II (low dose dexamethasone, physical activity)	Exercise Intervention	Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm II (low dose dexamethasone, physical activity)	Quality-of-Life Assessment	Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm I (high-dose dexamethasone, physical activity)	Exercise Intervention	Patients receive high-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm I (high-dose dexamethasone, physical activity)	Quality-of-Life Assessment	Patients receive high-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm II (low dose dexamethasone, physical activity)	Questionnaire Administration	Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm I (high-dose dexamethasone, physical activity)	Dexamethasone	Patients receive high-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.
Arm II (low dose dexamethasone, physical activity)	Dexamethasone	Patients receive low-dose dexamethasone PO BID for 7 days. Patients also follow a graded resistance exercise program 3 days a week and a walking regimen at least 5 days a week for 4 weeks. The frequency, duration, and intensity of the exercises will be evaluated and adjusted as necessary.

Primary Outcome Measures

Name	Time	Method
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and Day 29	Baseline, day 8, day 29	FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue) subscale is a 13 item subscale of FACT-G that allows patient to rate the intensity of their fatigue and its related symptoms on a scale of 0 (not at all) to 4 (very much). The total calculated score varied from 0-52 with a lower score indicating a more severe fatigue level. We measured the change in FACIT-F levels between Baseline and Day 8, and between Baseline and Day 29 using Wilcoxon signed rank test.

Secondary Outcome Measures

Name	Time	Method
Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total	Baseline, day 8, day 29	The PROMIS-F (Patient Reported Outcome Measurement Information System-Fatigue) short form was used to measure the experience of fatigue in patients' daily activities over the past week. It consists of 7 items with response options on a 5-point Likert scale, ranging from 1 (never) to 5 (always). We measured the change in PROMIS-F score between Baseline and Day 8, and between Baseline and Day 29 using Wilcoxon signed rank test. The total score is used in the analysis and is obtained by summing keyed scores of all items. Scores can range from 7 to 35, with higher scores indicating greater fatigue.
Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue	Baseline, day 8, day 29	ESAS (Edmonton Symptom Assessment Scale) is a validated scale ranging from 0 (not at all) to 10 (very much) used to assess 10 symptoms commonly experienced by cancer patients during the previous 24 hours: pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, sleep and feeling of wellbeing. We measured the change in ESAS fatigue score between Baseline and Day 8, and between Baseline and Day 29 using Wilcoxon signed rank test. Total ESAS fatigue score ranges from 0-10, with a higher score indicating higher fatigue.
Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score	Baseline, day 8, day 29	The MFSI-SF is a 30-item scale used to assess the multidimensional nature of fatigue. Responses are selected using a 5-point scale, ranging from 0 (not at all) to 4 (extremely fatigue). It consists of 5 subscales: general fatigue, physical fatigue, emotional fatigue, mental fatigue and vigor. The MFSI-SF total score is the sum of the general fatigue, physical fatigue, emotional fatigue and mental fatigue subscale score and subtracting vigor subscale score. Thus MFSI-SF total score ranges from 24-96, with a higher score indicating a higher fatigue level. We measured the change in MFSI-SF total score between Baseline and Day 8, and between Baseline and Day 29 using Wilcoxon signed rank test.