Methylphenidate and Exercise in Reducing Cancer-Related Fatigue in Patients With Prostate Cancer

Study Overview
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Brief Summary
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This phase II/III trial studies how well methylphenidate and exercise work in reducing cancer-related fatigue in patients with prostate cancer. Methylphenidate is a type of central nervous system stimulant that can improve cognitive ability, mainly in memory and cognitive function. Exercise can improve mood and the physical aspects of cancer-related fatigue. Giving methylphenidate in combination with exercise may work better in reducing cancer-related fatigue in patients with prostate cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine if the combination of exercise (EX) plus methylphenidate (MP) is superior to exercise plus placebo in the treatment of cancer-related fatigue (CRF) in patients with prostate cancer scheduled to receive radiotherapy with androgen deprivation therapy for 12 weeks. SECONDARY OBJECTIVE: I. To determine the effects of combined exercise plus methylphenidate on quality-of-life, mood, physical, and cognitive measures. EXPLORATORY OBJECTIVES: I. To identify potential synergistic effects of exercise and methylphenidate in improvement of CRF. II. To explore changes in brain activity by electroencephalography (EEG) in responders (with 4 point or greater change in Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scores) versus (vs) non-responders to the intervention. OUTLINE: Patients are randomized to 1 of 4 groups. GROUP I: Patients receive methylphenidate orally (PO) twice daily (BID) and undergo exercise program consisting of resistance training twice weekly (BIW) and walking 15- 40 minutes a day 4 days a week for 12 weeks. GROUP II: Patients receive a placebo PO BID and undergo exercise program consisting of resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks. GROUP III: Patients receive methylphenidate PO BID and undergo stretching for 4 days a week for 12 weeks. GROUP IV: Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12 weeks. After completion of study treatment, patients are followed up at 3 months.

Official Title
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A Combination Therapy to Treat Cancer-Related Fatigue - NCI R01

Conditions
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Prostate Carcinoma

Intervention / Treatment
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* Behavioral: Exercise Intervention
* Drug: Methylphenidate
* Other: Placebo
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Other: Stretching


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of prostate cancer and be scheduled to receive radiotherapy with concurrent androgen deprivation therapy, and presence of fatigue with severity of 1/10, on a 0-10 scale for at least 2 weeks Patient not regularly engaging in moderate aerobic exercise for >90 minutes/week and/or vigorous aerobic exercise for >30 minutes/week, and/ or strength training for >/= 1 day/week Have no clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of </=13 at baseline Be aged 18 years or older Be willing to engage in follow-up telephone calls with a research staff Be willing to participate in the exercise programs Have telephone access so they can be contacted by the research staff Have a hemoglobin level of >/= 10 g/dL within 2 weeks of enrollment Be able to understand the description of the study and give written informed consent Have a Zubrod performance status score of 0 to 2 Seen at an outpatient clinic at MD Anderson Cancer Center, its Houston Area Locations (HALs) or Smith Radiation Oncology Clinic (HHS) Exclusion Criteria: Have a major contraindication to MethylphenidateMP) (e.g., allergy/hypersensitivity to study medications or their constituents), exercise (e.g., cardiac disease), or conditions making adherence difficult as determined by the attending physician Be currently taking MP, or have taken it within the previous 10 days Be unable to complete the baseline assessment forms (e.g., due to language or sensory barriers) or to understand the recommendations for participation in the study Need monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine Have glaucoma Have severe cardiac disease (New York Heart Association functional class III or IV) Have tachycardia and/or uncontrolled hypertension Be currently receiving anticoagulants, anticonvulsants (phenobarbital, diphenylhydantone, primidone), phenylbutazone, and/or tricyclic drugs (imipramine, clomipramine, or desipramine).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (methylphenidate, resistance training, walking)<br>Patients receive methylphenidate PO BID and undergo exercise program consisting of resistance training BIW and walking 15- 40 minutes a day 4 days a week for 12 weeks. | Behavioral: Exercise Intervention<br>* Undergo resistance training and walking<br>Drug: Methylphenidate<br>* Given PO<br>* Other names: Daytrana;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Group II (placebo, resistance training, stretching)<br>Patients receive a placebo PO BID and undergo exercise program consisting of resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks. | Behavioral: Exercise Intervention<br>* Undergo resistance training and walking<br>Other: Placebo<br>* Given PO<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Group III (methylphenidate, stretching)<br>Patients receive methylphenidate PO BID and undergo stretching for 4 days a week for 12 weeks. | Drug: Methylphenidate<br>* Given PO<br>* Other names: Daytrana;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Stretching<br>* Undergo stretching<br>|
| Active Comparator: Group IV (placebo, stretching)<br>Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12 weeks. | Other: Placebo<br>* Given PO<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Stretching<br>* Undergo stretching<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of cancer-related fatigue in all groups | Will measure cancer-related fatigue (CRF) using the area under the curve (AUC) of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale score. The intervention exposure will be operationalized as proportion of the total minutes of prescribed exercise intervention the study patient was actually able to participate, or the proportion of prescribed study medication the study patient was able to actually take. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life, mood, physical and cognitive measures in all groups | Will use a mixed-effects model to compare changes in Functional Assessment of Cancer Therapy - General (FACT-G), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF), Hospital Anxiety and Depression Scale (HADS), usual gait speed, hand grip strength (HGS), 30 second chair stand test (30s-CST), actigraphy, VO2 max, and C-reactive protein scores over time between the four treatment groups. For the mixed effects model, we will estimate the slopes for the changes in scores over time for each group and test the difference in these slopes. | Baseline up to 12 weeks |