A Home-Based Prehabilitation Exercise Intervention for Improving Physical Function in Patients Receiving Chemotherapy Before Radical Cystectomy, Get Moving Trial

Study Overview
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Brief Summary
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Prehabilitation refers to the process of improving a patient's functional capabilities prior to a surgical procedure with the goal of decreasing post-surgical inactivity and physical decline. This clinical trial evaluates the utility of a personalized home-based prehabilitation exercise intervention for the improvement of physical function and surgical outcomes in patients receiving chemotherapy before routine radical cystectomy for localized (non-metastatic) muscle-invasive bladder cancer. The exercise intervention includes at-home exercise sessions focused on the improvement of core strength and balance as well as personalized step count goals, delivered to patients remotely via a smart-device-based application (ExerciseRx). Encouraging physical activity before surgery may improve physical function and surgical outcomes in patients who are scheduled to undergo surgery for their non-metastatic muscle-invasive bladder cancer.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 arms and are followed from enrollment through neoadjuvant chemotherapy receipt, radical cystectomy, and for 90 days following surgery (total estimated time on study:  7 months) ARM A: Patients use the ExerciseRx application (app) to follow the (P)REHAB exercise program, which consists of four 20-30 minute home exercise sessions per week and personalized step count goal setting and tracking, while receiving standard of care (SOC) NAC prior to SOC radical cystectomy (RC), and for 90 days following surgery. Patients also wear a FitBit and use the FitBit app on study. ARM B: Patients receive SOC educational materials and wear a FitBit and use the FitBit app while receiving SOC NAC prior to SOC RC. After completion of study intervention, patients are followed up at 90 days following SOC RC.

Official Title
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The Get Moving Trial: A Phase I/II RCT of Home-Based (P)Rehabilitation With ExerciseRx in Muscle-Invasive Bladder Cancer

Conditions
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Stage IIIA Bladder Cancer AJCC v8, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8

Intervention / Treatment
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* Other: Best Practice
* Other: Exercise Intervention
* Other: App-Based Intervention
* Other: App-Based Intervention
* Other: Interview
* Other: Wearable Activity Tracker
* Other: Physical Performance Testing
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older English-speaking Diagnosis of American Urological Association (AUA) nonmetastatic muscle-invasive bladder cancer (MIBC) (e.g. American Joint Committee on Cancer [AJCC] pT2-4 N0-1 M0) Patients who have been indicated for cisplatin-based NAC followed by RC in shared-decision-making with their primary urologist and medical oncologist Have a smart device meeting study criteria or willing to use a study-supplied smart device Willing and able to participate in trial activities Able to understand and willing to sign written informed consent in English Exclusion Criteria: Cognitive/mental impairment that will preclude ability to participate in routine exercise activities. Significant cognitive or memory impairment or baseline dementia that would preclude a patient's ability to follow instructions or reproduce exercises as characterized by scoring < 24 on the Minimental Status Examination Immobility, inability/unwillingness to perform personalized exercise program. Inability to perform exercises safely from seated or standing position at home or recent falls or high fall risk. Neurologic or orthopedic condition that restricts participation in unsupervised home exercises, such as prior stroke with neurologic impairment, weight bearing precautions, unwillingness to participate in exercises Participants who have nonmuscle-invasive bladder cancer, or radiographic evidence of metastatic disease involving other organs including brain metastases. Patients with predominant histology other than urothelial carcinoma of the bladder who would not otherwise be considered candidates for NAC or RC Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A ([P]REHAB intervention)<br>Patients use the ExerciseRx app to follow the (P)REHAB exercise program, which consists of four 20-30 minute home exercise sessions per week and personalized step count goal setting and tracking, during receipt of SOC NAC prior to SOC RC and for 90 days following surgery (total  7 months). Patients also download the FitBit app and wear a FitBit throughout the study. | Other: Exercise Intervention<br>* Receive (P)REHAB exercise program<br>Other: App-Based Intervention<br>* Use ExerciseRx app<br>Other: App-Based Intervention<br>* Use FitBit app<br>Other: Interview<br>* Ancillary studies<br>Other: Wearable Activity Tracker<br>* Wear FitBit<br>Other: Physical Performance Testing<br>* Ancillary studies<br>* Other names: Physical Function Testing;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm B (standard of care)<br>Patients receive SOC educational materials and wear a FitBit and use the FitBit app during receipt of SOC NAC prior to SOC RC and for 90 days following surgery (total  7 months). | Other: Best Practice<br>* Receive SOC educational materials<br>* Other names: standard therapy;Other: App-Based Intervention<br>* Use FitBit app<br>Other: Wearable Activity Tracker<br>* Wear FitBit<br>Other: Physical Performance Testing<br>* Ancillary studies<br>* Other names: Physical Function Testing;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in physical function | Physical function will be measured by the Short Performance Physical Battery (SPPB). Change in physical function will be measured and compared between the (P)REHAB and standard of care arms. SPPB scores range from zero to 12 possible points. SPPB score of 3-9 points in persons with possible sarcopenia but no mobility disability indicates frailty; SPPB score of 10 or greater for persons with no sarcopenia and no mobility disability indicates robustness. Persons with a score of 2 or lower who have sarcopenia, potential cachexia, and mobility disability are determined to be disabled. | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| Change in physical function | Physical function will be measured by the Short Performance Physical Battery (SPPB). Change in physical function will be measured and compared between the (P)REHAB and standard of care arms. SPPB scores range from zero to 12 possible points. SPPB score of 3-9 points in persons with possible sarcopenia but no mobility disability indicates frailty; SPPB score of 10 or greater for persons with no sarcopenia and no mobility disability indicates robustness. Persons with a score of 2 or lower who have sarcopenia, potential cachexia, and mobility disability are determined to be disabled. | From 3-4 months post enrollment (after NAC and before RC) (T2) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Change in physical function | Physical function will be measured by the Short Performance Physical Battery (SPPB). Change in physical function will be measured and compared between the (P)REHAB and standard of care arms. SPPB scores range from zero to 12 possible points. SPPB score of 3-9 points in persons with possible sarcopenia but no mobility disability indicates frailty; SPPB score of 10 or greater for persons with no sarcopenia and no mobility disability indicates robustness. Persons with a score of 2 or lower who have sarcopenia, potential cachexia, and mobility disability are determined to be disabled. | From enrollment (T1) to 6-7 months post enrollment (90 days post RC) (T3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial recruitment | Trial recruitment (proportion enrolled versus eligible, reason for not enrolling) will be described via qualitative report. | At enrollment | 
| Trial retention | Trial retention (proportion retained versus all enrolled, reason for not completing) will be described via qualitative report. Successful retention is defined as continued participation within the trial until T3. | Through study completion, on average 7 months | 
| Protocol adherence | Protocol adherence (proportion adhered versus all enrolled, specifics for how protocol was not followed and why) will be described via qualitative report. Protocol adherence for the (P)REHAB arm is defined as completion of >=70% of all exercise activities (goal 4x weekly, 20-30min/session) as measured using the ExerciseRx app. | Through study completion, on average 7 months | 
| Patient experience with use of ExerciseRx app, including app engagement ([P]REHAB arm only) (feasibility) | Qualitative experience will be assessed by Zoom interviews (usability interview) with a subset of volunteer participants from the (P)REHAB arm and app engagement will be assessed by an affinity analysis of the MAUQ | Through study completion, on average 7 months | 
| Frailty | Frailty will be assessed using the Cancer and Aging Resilience Geriatric Assessment. | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| Frailty | Frailty will be assessed using the Cancer and Aging Resilience Geriatric Assessment. | From 3-4 months post enrollment (after NAC and before RC) (T2) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Frailty | Frailty will be assessed using the Cancer and Aging Resilience Geriatric Assessment. | From enrollment (T1) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Body composition - fat free mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating the skeletal muscle index and fat mass index of deidentified computed tomography scans. | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| Body composition - fat free mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating the skeletal muscle index and fat mass index of deidentified computed tomography scans. | From 3-4 months post enrollment (after NAC and before RC) (T2) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Body composition - fat free mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating the skeletal muscle index and fat mass index of deidentified computed tomography scans. | From enrollment (T1) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Body composition - fat mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating fat mass index of deidentified computed tomography scans. | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| Body composition - fat mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating fat mass index of deidentified computed tomography scans. | From 3-4 months post enrollment (after NAC and before RC) (T2) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Body composition - fat mass | Body composition will be measured using a validated, supervised machine learning body composition segmentation algorithm evaluating fat mass index of deidentified computed tomography scans. | From enrollment (T1) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Patient-reported health-related quality of life | Patient reported health-related quality of life will be assessed by a change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30. All of the subscales and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Values represent absolute changes from week 1 to 6 of treatment. | At enrollment, 3-4 months from enrollment (after NAC and before RC), 6-7 months from enrollment (90 days post RC) | 
| Patient-reported health-related quality of life - bladder cancer specific | Bladder cancer-specific patient-reported health-related quality of life will be assessed by a change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-Bladder Cancer Muscle-Invasive 30). All subscale and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Values represent absolute changes from week 1 to 6 of treatment. | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| Patient-reported health-related quality of life - bladder cancer specific | Bladder cancer-specific patient-reported health-related quality of life will be assessed by a change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-Bladder Cancer Muscle-Invasive 30). All subscale and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Values represent absolute changes from week 1 to 6 of treatment. | From 3-4 months post enrollment (after NAC and before RC) (T2) to 6-7 months post enrollment (90 days post RC) (T3) | 
| Patient-reported health-related quality of life - bladder cancer specific | Bladder cancer-specific patient-reported health-related quality of life will be assessed by a change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-Bladder Cancer Muscle-Invasive 30). All subscale and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Values represent absolute changes from week 1 to 6 of treatment. | From enrollment (T1) to 6-7 months post enrollment (90 days post RC) (T3) | 
| NAC-associated adverse events | Will be recorded as both physician-reported adverse events utilizing Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 5.0 and using the patient-reported CTCAE and will be described via qualitative report | From enrollment (T1) to 3-4 months post enrollment (after NAC and before RC) (T2) | 
| (P)REHAB-associated adverse events | Will be assessed by comparing physician-reported CTCAE v. 5.0 adverse events (e.g. falls, pain score as measured using a visual analog scale 0-10, and fatigue), compared between the (P)REHAB and standard of care arms. | At enrollment (T1), 3-4 months from enrollment (after NAC and before RC) (T2), 6-7 months from enrollment (90 days post RC) (T3) | 
| Number of participants with post-surgical complications within 90 days graded using the Clavien grading scale | Graded using the Clavien grading scale and reported qualitatively. The Clavien-Dindo Classification is a grading system used throughout surgery for classifying adverse events (complications) that occur as a result of surgical procedures. The system consists of five (I, II, III, IV and V) or seven (I, II, IIIa, IIIb, IVa, IVb and V) grades of severity, with Grade I being low and Grade V being death. | Within 90 days of RC | 
| Surgical outcomes - length of stay | Surgical outcomes include length of stay following RC. Surgical outcomes will be reported via qualitative report | Through study completion, on average 7 months | 
| Surgical outcomes - post discharge disposition | Surgical outcomes include discharge disposition (e.g. discharge to home vs. short term nursing facility versus rehabilitation unit). For patients not discharged to home, will evaluate length of time in a skilled nursing facility or rehabilitation unit as necessary. Surgical outcomes will be reported via qualitative report | Through study completion, on average 7 months | 
| Average daily step count | Number of steps per day as measured by the FitBit wearable will be reported. | Through study completion, on average 7 months | 
| Average daily sedentary time | Average daily sedentary time as measured by the FitBit wearable will be reported. | Through study completion, on average 7 months |