Researching the Effect of Exercise on Cancer

Study Overview
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Brief Summary
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Researchers think that exercise may be able to prevent cancer from coming back by lowering ctDNA levels. The purpose of this study is to explore how aerobic exercise (exercise that stimulates and strengthens the heart and lungs and improves the body's use of oxygen) can reduce the level of ctDNA found in the blood. During the study, the highest level of exercise that is practical, is safe, and has positive effects on the body that may prevent the return of cancer (including a decrease in ctDNA levels) will be found. Each level of exercise tested will be a certain number of minutes each week. Once the best level of exercise is found, it will be tested further in a new group of participants. All participants in this study will have been previously treated for breast, prostate, or colorectal cancer.

Official Title
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Phase 1a/b Trial of Exercise as Interception Therapy for Primary High-Risk Cancer

Conditions
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Breast Cancer, Prostate Cancer, Colorectal Cancer, Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, Stage I Prostate Cancer, Stage II Prostate Cancer, Stage III Prostate Cancer, Stage I Colorectal Cancer, Stage II Colorectal Cancer, Stage III Colorectal Cancer

Intervention / Treatment
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* Other: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postsurgical diagnosis of high-risk colorectal cancer or high-risk breast cancer as defined by one of the following: ° High-risk colorectal cancer Stage 3 or ctDNA positive ° High-risk breast cancer Residual invasive disease in the breast or the lymph nodes following completion of neoadjuvant chemotherapy (NACT), Estrogen receptor (ER), and/or progesterone receptor (PR) positive and HER2 negative, CPS-EG score ≥ 3, CPS-EG score ≥2 w ith ypN+, or Recurrence score ≥ 25 No evidence of disease Age ≥ 18 Interval of ≥ 1 month but ≤ 2 years following completion of all definitive adjuvant therapy Non-exercising (i.e., < 30 mins of moderate and < 20 mins of vigorous exercise/wk), as assessed by remote activity and heart rate tracking for a 7-day period prior to study entry) Cleared for exercise participation as per screening clearance via PAR-Q+ Willingness to comply with all study-related procedures Exclusion Criteria: Enrollment onto any other interventional investigational study except interventions determined by the PI not to confound study outcomes Any other current diagnosis of invasive cancer of any kind Distant metastatic malignancy of any kind Any other condition or intercurrent illness that, in the opinion of the investigator, makes the subject a poor candidate for study participation

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: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-Finding/Escalation<br>Fifty (n=50) post-treatment patients with colorectal cancer or breast cancer, deemed high-risk of relapse. The study will use an adaptive continuous reassessment method (CRM) design to assign patients sequentially at trial entry to one of five escalated doses depending on the feasibility / tolerability of exercise therapy evaluated over the total treatment period. The primary objective of this phase 1a trial is to identify the RP2D of exercise therapy for further evaluation in the phase 1b trial. | Other: Exercise<br>* Exercise therapy in both phases will consist of individualized walking delivered 3 to 6 times weekly (over a 7-day period). Exercise treatment will be delivered for up to 18 months, or until progression of disease or withdrawal of consent, whichever comes first. The phase 1a trial will assess five doses of exercise therapy (i.e., 90, 150, 225, 300, and 375 mins/wk) delivered following a non-linear (i.e., exercise dose is continually altered and progressed in conjunction with appropriate rest/recovery sessions across the entire intervention period) dosing schedule. The phase 1b trial will only test one dose of exercise therapy - the RP2D identified in the phase 1a trial.<br>|
| Experimental: Dose Expansion<br>An independent cohort of 30 post-treatment patients with colorectal (n=15) or breast (n=15) cancer deemed high-risk of relapse. This cohort expansion trial will only evaluate the RP2D identified in the phase 1a trial. The primary objective of this phase 1b trial is to further evaluate the feasibility, safety, and biological activity of the RP2D. | Other: Exercise<br>* Exercise therapy in both phases will consist of individualized walking delivered 3 to 6 times weekly (over a 7-day period). Exercise treatment will be delivered for up to 18 months, or until progression of disease or withdrawal of consent, whichever comes first. The phase 1a trial will assess five doses of exercise therapy (i.e., 90, 150, 225, 300, and 375 mins/wk) delivered following a non-linear (i.e., exercise dose is continually altered and progressed in conjunction with appropriate rest/recovery sessions across the entire intervention period) dosing schedule. The phase 1b trial will only test one dose of exercise therapy - the RP2D identified in the phase 1a trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify the recommended phase 2 dose (RP2D) of exercise for testing in the phase 1b. | Using an adaptive phase 1 (non-randomized) design, non-exercising (i.e., <60 mins/wk of moderate or vigorous exercise) post-treatment patients with primary breast, prostate, or colorectal cancer and detectable ctDNA (n=50) will be administered one of five escalating dose levels. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Memorial Sloan Kettering Cancer Center, Breast Cancer, Prostate Cancer, Colorectal Cancer, exercise, ctDNA, 20-378