Advanced Malignant Neoplasm, Fatigue, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm, Refractory Malignant Neoplasm
Conditions
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.
Interventions
DRUGDexamethasone
Given PO
BEHAVIORALExercise Intervention
Complete a graded resistance exercise program and a walking regimen
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSriram Yennu
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Patients were recruited from MD Anderson Cancer Center outpatients clinic for supportive are who has a diagnosis of advanced cancer with average intensity of fatigue of \>=4/10 on the ESAS scale in the previous 24 hours and presence of fatigue for at least 2 weeks.
Pre-assignment details
A total of 90 patients were enrolled for this study. Of them 7 withdrew their consent, Doctor did not allow Dexamethasone for 3 cases, 2 had disease progression, and for 2 cases, their oncologist did not approve it. Thus a total of 76 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Physical Exercise + Low Dose Dexamethasone Received stabdardizex Physical activity for 4 weeks and 4mg of Dexamethasone orally twice daily for 7 days | 31 |
| Physical Exercise + High Dose Dexamethasone Received stabdardizex Physical activity for 4 weeks and 8mg of Dexamethasone orally twice daily for 7 days | 29 |
| Total | 60 |
Baseline characteristics
| Characteristic | Physical Exercise + High Dose Dexamethasone | Total | Physical Exercise + Low Dose Dexamethasone |
|---|---|---|---|
| Age, Continuous | 58 years | 60 years | 60 years |
| Assessment Edmonton Symptom Assessment System (ESAS) Fatigue Score | 6 units on a scale | 6 units on a scale | 6 units on a scale |
| Assessment Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) subscale | 20 units on a scale | 21 units on a scale | 23 units on a scale |
| Assessment Hospital Anxiety and Depression Scale (HADS) Anxiety | 5 units on a scale | 5 units on a scale | 4 units on a scale |
| Assessment Hospital Anxiety and Depression Scale (HADS) Depression | 7 units on a scale | 6 units on a scale | 6 units on a scale |
| Cancer Diagnosis Breast | 7 Participants | 14 Participants | 7 Participants |
| Cancer Diagnosis Gastrointestinal | 5 Participants | 14 Participants | 9 Participants |
| Cancer Diagnosis Genitourinary | 6 Participants | 14 Participants | 8 Participants |
| Cancer Diagnosis Lung | 3 Participants | 7 Participants | 4 Participants |
| Cancer Diagnosis Other | 8 Participants | 11 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 54 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 55 Participants | 28 Participants |
| Region of Enrollment United States | 29 participants | 60 participants | 31 participants |
| Sex: Female, Male Female | 15 Participants | 31 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 29 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 1 / 29 |
| other Total, other adverse events | 0 / 31 | 0 / 29 |
| serious Total, serious adverse events | 5 / 31 | 4 / 29 |
Outcome results
Primary
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and 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.
Time frame: Baseline, day 8, day 29
Population: Participants who completed the intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Physical Exercise + Low Dose Dexamethasone | Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and Day 29 | Change between Baseline and Day 8 | 9 score on a scale |
| Physical Exercise + Low Dose Dexamethasone | Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and Day 29 | Change between Baseline and Day 29 | 10 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and Day 29 | Change between Baseline and Day 8 | 8 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Levels at Day 8 and Day 29 | Change between Baseline and Day 29 | 12 score on a scale |
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue
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.
Time frame: Baseline, day 8, day 29
Population: Participants who completed the intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Physical Exercise + Low Dose Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue | Change between Baseline and Day 8 | -1.5 score on a scale |
| Physical Exercise + Low Dose Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue | Change between Baseline and Day 29 | -1.5 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue | Change between Baseline and Day 8 | -2 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Fatigue | Change between Baseline and Day 29 | -3 score on a scale |
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.065Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score
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.
Time frame: Baseline, day 8, day 29
Population: Participants who completed the intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Physical Exercise + Low Dose Dexamethasone | Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score | Change between Baseline and Day 8 | -9 score on a scale |
| Physical Exercise + Low Dose Dexamethasone | Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score | Change between Baseline and Day 29 | -6 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score | Change between Baseline and Day 8 | -5 score on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI_SF) Total Score | Change between Baseline and Day 29 | -4.5 score on a scale |
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: =0.3Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 8p-value: =0.19Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: =0.27Wilcoxon (Mann-Whitney)
Secondary
Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total
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.
Time frame: Baseline, day 8, day 29
Population: Participants who completed the intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Physical Exercise + Low Dose Dexamethasone | Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total | Change between Baseline and Day 8 | -3 units on a scale |
| Physical Exercise + Low Dose Dexamethasone | Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total | Change between Baseline and Day 29 | -9 units on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total | Change between Baseline and Day 8 | -4 units on a scale |
| Physical Exercise + High Dose Dexamethasone | Change in Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Total | Change between Baseline and Day 29 | -7 units on a scale |
Comparison: Change between Baseline and Day 8p-value: =0.003Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 8p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Change between Baseline and Day 29p-value: <0.001Wilcoxon (Mann-Whitney)