Exercise in Metastatic Breast Cancer: EMBody

Study Overview
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Brief Summary
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The purpose of this study is to study exercise in a novel population with indolent MBC (no progression on current therapy in prior 12 months and not receiving cytotoxic chemotherapy). The study team hypothesizes that delivering virtual, supervised, progressive intensity aerobic and resistance training exercise for 16 weeks in this population will significantly improve 1) cardiorespiratory fitness, functional status, and sarcopenia (low muscle mass), all established predictors of survival, and 2) patient- reported outcomes.

Detailed Description
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This is a randomized, two arm, single-center study designed to compare the effect of exercise versus usual care control on the clinical parameter of cardiorespiratory fitness, in patients with metastatic breast cancer with indolent disease biology over a 16-week period. This study will be enrolling up to 100 participants. Participants will be randomized 1:1 in blocks of 4 to the exercise intervention or usual care, stratified by frailty yes/no defined by baseline SPPB score ≤ 8 or > 8. Primary Objective To compare the effect of a 16-week multimodality, virtually delivered exercise intervention on cardiorespiratory fitness measured by a modified Bruce ramp protocol treadmill test to usual care, in patients with indolent metastatic breast cancer. Secondary Objectives To compare the effect of exercise versus usual care on objective physical function measured by the short physical performance battery (SBBP) To compare the effect of exercise versus usual care on subjective physical functioning measured by PROMIS-29 questionnaire To compare the effect of exercise versus usual care on body composition, measured by visceral adiposity, lean muscle mass, and muscle density on CT scans obtained as standard of care using SliceOmatic software To compare the effect of exercise versus usual care on objective physical activity measured by accelerometer wear To compare the effect of exercise versus usual care on patient reported outcomes, including fatigue (BFI) and health related quality of life (PROMIS-29) To determine the fidelity of the exercise intervention, measured by changes in measures of constructs of habit and intention administered by questionnaire To describe patient uptake and adherence with the intervention, measured by proportion of approached patients who consent to the study, and proportion of assigned training sessions attended by patients randomized to the exercise arm.

Official Title
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Exercise in Metastatic Breast Cancer: EMBody

Conditions
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Breast Cancer, Indolent Metastatic Breast Cancer

Intervention / Treatment
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* Behavioral: Exercise Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Diagnosis of metastatic breast cancer No progression of disease in the 12 months prior to screening per the treating investigator If participant has changed treatments in the prior 12 months for reasons other than progressive disease, they remain eligible Participants on no treatment or no evidence of disease but still with a diagnosis of metastatic breast cancer are eligible ECOG performance status of 0-2 Participants must be able to march in place for 30 seconds. Assistance by holding onto a chair is allowed. Informed consent and authorization of the release of health information must be obtained according to institutional guidelines Currently not meeting physical activity guidelines (defined as less than 150 minutes of moderate to vigorous exercise per week measured by the RPAQ questionnaire administered during screening) Exclusion Criteria: Receiving cytotoxic chemotherapy at any point in the prior 12 months. Participants receiving endocrine therapy are eligible. Participants receiving targeted therapy or antibody therapy are eligible (examples including trastuzumab, pertuzumab, TDM-1, trastuzumab deruxtecan, sacituzumab govetecan, immunotherapy, CDK4/6 inhibitors, olaparib, alpelisib, etc.) Any condition precluding supervised exercise participation. A letter from a physician supporting participation can supercede this eligibility criteria. NYHA class III or IV congestive heart failure Uncontrolled angina Myocardial infarction in the prior 12 months Orthopedic surgery in the previous 3 months or plans for orthopedic surgery during the study period Chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen Symptomatic peripheral vascular disease Or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator, including psychological illness. Active, untreated brain metastases

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Intervention<br>Eligible and consented participants randomized to the exercise arm (EX) will work with an exercise trainer 3x weekly for 16 weeks. Training sessions are 60 min. Schedules are determined by participant and trainer with oversight by the study team, ideally occurring at similar times each day in line with IBC theory. Each training session will be delivered virtually over a HIPAA compliant IU Health Zoom platform. The virtual exercise sessions include 3 parts: cardiovascular exercise, resistance training, and balance or stretching exercise. During sessions, patients will wear provided heart rate monitors with a training goal of moderate intensity, defined as 40-60% of heart rate reserve. Based on the participant's rate of perceived exertion (RPE), heart rate, and individual response during each session, trainers will follow an algorithm designed by the PI and collaborators to progress or regress intensity level. Participant will attend a class on creating and maintaining behavior changes. | Behavioral: Exercise Intervention<br>* Eligible and consented participants randomized to the exercise arm (EX) will work with an exercise trainer 3x weekly for 16 weeks. Training sessions are 60 min. Schedules are determined by participant and trainer with oversight by the study team, ideally occurring at similar times each day in line with IBC theory. Each training session will be delivered virtually over a HIPAA compliant IU Health Zoom platform. The virtual exercise sessions include 3 parts: cardiovascular exercise, resistance training, and balance or stretching exercise. During sessions, patients will wear provided heart rate monitors with a training goal of moderate intensity, defined as 40-60% of heart rate reserve. Based on the participant's rate of perceived exertion (RPE), heart rate, and individual response during each session, trainers will follow an algorithm designed by the PI and collaborators to progress or regress intensity level. Participant will attend a class on creating and maintaining behavior changes.<br>|
| No Intervention: Usual Care<br>Participants randomized to usual care (UC) will receive care per their treatment team. UC participants are encouraged to exercise but will not be provided components of the intervention. Participants in the UC arm will be given usual care handouts at baseline from the American College of Sports Medicine. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiorespiratory fitness | Measured by minutes on the treadmill | baseline, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| physical performance battery | total score on short physical performance battery | baseline, 8, and 16 weeks | 
| Mean quality of life, as measured by the Patient-Reported Outcomes Measurement Information System-29 | Likert-scaled questionnaire, with response scores ranging from 1 to 5. Scores alternate from 1 or 5 being the lowest value. | baseline, 8, and 16 weeks | 
| muscle mass | measured by mg/kg2 on HU on CT scans | baseline, and 16 weeks | 
| muscle density | measured by mg/kg2 on HU on CT scans | baseline, and 16 weeks | 
| adipose mass | measured by mg/kg2 on HU on CT scans | baseline, and 16 weeks | 
| Change in physical activity minutes | measured by accelerometer data | baseline to post 16-week intervention | 
| Change in steps per day | measured by accelerometer data | baseline to post 16-week intervention | 
| Mean fatigue score as measured by the basic fatigue inventory (BFI) | Likert-scaled questionnaire, with response scores ranging from 0 to 10, with 10 being the worse response. | baseline, and16-weeks | 
| Change intention and habits, as measured by the Behavioral Theory Scales | Likert-scaled questionnaire, measured with a 5-point Likert scale with response options ranging from strongly disagree to strongly agree. Total scores are summed in the range of 40 to 200, with a higher score indicating stronger motivation that could predict exercise behavior. | baseline, and 16-weeks | 
| Uptake of the study | the proportion of total patients approached, screened, and ultimately completing the baseline assessments | date open to accrual until closed to accrual, up to 5 years | 
| Adherence with the intervention defined | the proportion of scheduled sessions attended by participants randomized to the exercise intervention arm | baseline to post 16-week intervention | 
| change in patient-reported functional limitations, as measured by a functional limitations scale | mean score of 5 question scale, where participants responses are either scored 0 or 1, with some difficulty a 1 and no difficulty as a 0. | baseline, and16-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, indolent metastatic breast cancer, exercise