Aerobic Exercise in Changing Biomarkers in Patients with Solid Tumors or Clonal Hematopoiesis
This clinical trial studies the effect of aerobic exercise in changing biomarkers in patients with solid tumors or clonal hematopoiesis, a condition in which some of the patients' blood cells have a different genetic pattern than the rest of the blood cells. Aerobic exercise stimulates and strengthens the heart and lungs, and improves the body’s use of oxygen. This may help prevent or slow the growth of tumors by changing the biomarkers (signs of disease) found in the blood or by preventing recurrence of certain cancers.
Inclusion Criteria
- COHORT 1 (CH): CH called by Memorial Sloan Kettering (MSK) practices as documented by an MSK physician
- COHORT 1 (CH): Age >= 18 yrs
- COHORT 1 (CH): Completion of all anticancer therapy
- COHORT 1 (CH): High risk of cardiovascular disease defined by presence of at least one of the following: * Age >= 60 * Prior treatment with chemotherapy * Prior left-sided breast and/or chest wall radiotherapy * Currently receiving or previously received androgen deprivation therapy * Prior bone marrow transplant * History of smoking * Currently treated for one or more cardiovascular risk factors (i.e., hypertension, diabetes, hyperlipidemia)
- COHORT 1 (CH): Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 1 (CH): Willingness to comply with all study-related procedures
- COHORT 2 (SOLID TUMOR): Patients at risk of harboring circulating tumor DNA as defined by one of the following: * Histologically confirmed stage III (i.e., high risk of recurrence) colorectal cancer within 2 years of completion of all adjuvant therapy * Histologically confirmed stage III breast cancer with residual disease after neoadjuvant therapy and within 12 months of completing (neo)adjuvant chemotherapy * Patients with metastatic breast cancer and radiographic stable disease or no evidence of disease (NED) for >= 6 months and not currently receiving chemotherapy (endocrine therapy and anti-HER2 antibodies allowed)
- COHORT 2 (SOLID TUMOR): Age >= 18 yrs
- COHORT 2 (SOLID TUMOR): Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 2 (SOLID TUMOR): Willingness to comply with all study-related procedures
- COHORT 3 (ACTIVE SURVEILLANCE): Men with histologically confirmed localized prostate cancer undergoing active surveillance
- COHORT 3 (ACTIVE SURVEILLANCE): Age >= 18 yrs
- COHORT 3 (ACTIVE SURVEILLANCE): Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 3 (ACTIVE SURVEILLANCE): Willingness to comply with all study-related procedures
- COHORT 3 (ACTIVE SURVEILLANCE): Cleared for exercise participation as per pre-screening clearance via Physical Activity Readiness Questionnaire (PAR-Q+)
- COHORT 4 (LYNCH SYNDROME): Age >= 18 yrs
- COHORT 4 (LYNCH SYNDROME): Hereditary colorectal cancer syndrome, specifically Lynch syndrome, defined by the presence of a deleterious germline mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes
- COHORT 4 (LYNCH SYNDROME): Have a portion of the distal colon or rectosigmoid intact to enable collection of normal mucosa biopsies
- COHORT 4 (LYNCH SYNDROME): Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 4 (LYNCH SYNDROME): Willingness to comply with all study-related procedures
- COHORT 4 (LYNCH SYNDROME): Cleared for exercise participation as per pre-screening clearance via PAR-Q+
- COHORT 5 (EDD) PHASE 0A: Age ≥ 18 yrs
- COHORT 5 (EDD) PHASE 0A: Receiving investigational agent under an EDD protocol for at least 2 months
- COHORT 5 (EDD) PHASE 0A: Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 5 (EDD) PHASE 0A: Willingness to comply with all study-related procedures
- COHORT 5 (EDD) PHASE 0A: Cleared for exercise participation as per pre-screening clearance via PAR-Q+
- COHORT 5 (EDD) PHASE 0B: Age ≥ 18 yrs
- COHORT 5 (EDD) PHASE 0B: Newly initiating investigational agent on an EDD service protocol
- COHORT 5 (EDD) PHASE 0B: Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
- COHORT 5 (EDD) PHASE 0B: Willingness to comply with all study-related procedures
- COHORT 5 (EDD) PHASE 0B: Cleared for exercise participation as per pre-screening clearance via PAR-Q+
Exclusion Criteria
- Concurrent use of any form of antitumor therapy (endocrine therapy and anti-HER2 antibodies allowed)
- Enrollment onto any other interventional investigational study except interventions determined by the PI not to confound study outcomes (does not apply to Cohort 5: EDD)
- Any other condition or intercurrent illness that, in the opinion of the investigator, makes the subject a poor candidate for study participation
- Mental impairment leading to inability to cooperate
- Any of the following contraindications to cardiopulmonary exercise testing (Cohorts 1 and 2 only): * Acute myocardial infarction within 3–5 days of any planned study procedures * Unstable angina * Uncontrolled arrhythmia causing symptoms or hemodynamic compromise * Recurrent syncope * Active endocarditis * Acute myocarditis or pericarditis * Symptomatic severe aortic stenosis * Uncontrolled heart failure * Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures * Thrombosis of lower extremities within 3 months of any planned study procedures * Suspected dissecting aneurysm * Uncontrolled asthma * Pulmonary edema * Respiratory failure * Acute non-cardiopulmonary disorders that may affect exercise performance
- Room air desaturation at rest =< 85% (Cohorts 1 and 2 only)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03996239.
PRIMARY OBJECTIVES:
I. To explore the biological activity of exercise as evaluated by changes in clonal hematopoiesis (CH) burden quantified by the variant allele frequency (VAF) of CH mutations (measured by targeted CH panel in peripheral blood). (Cohort 1 [CH])
II. To explore the biological activity of exercise as evaluated by changes in residual tumor burden quantified by the amount of circulating tumor deoxyribonucleic acid (DNA) (ctDNA). (Cohort 2 [solid tumor])
III. To explore the biological activity of exercise therapy as evaluated by changes in CH burden quantified by the variant allele frequency (VAF) of CH mutations (measured by targeted CH panel in peripheral blood). (Cohort 3 [active surveillance])
IV. To explore the safety and tolerability of exercise in individuals with Lynch Syndrome undergoing surveillance by the Memorial Sloan Kettering (MSK) Genetics Service. (Cohort 4 [Lynch syndrome])
V. To evaluate the feasibility of exercise therapy by week 6 in patients receiving an investigational treatment in an Early Drug Development (EDD) Service protocol for at least 2 months. (Phase 0a) (Cohort 5 [EDD])
VI. To explore the feasibility of exercise therapy by week 8 in patients newly initiating an investigational therapy in an EDD Service protocol. (Phase 0b) (Cohort 5 [EDD])
SECONDARY OBJECTIVES:
I. To explore the pharmacodynamics of exercise as evaluated by changes in physiological correlates (e.g., exercise capacity, body weight, blood pressure, arterial stiffness) and circulating factors (e.g., pro-inflammatory cytokines, proteomics, metabolomics). (Cohort 1)
II. To assess safety and tolerability. (Cohorts 1, 2, and 3)
III. To explore the effect on tumor genetic landscape by tracking non-synonymous somatic mutations identified in baseline ctDNA. (Cohort 2)
IV. To explore the effects on CH burden. (Cohort 2)
V. To explore the pharmacodynamics of exercise as evaluated by changes in physiological correlates (e.g., exercise capacity, body weight, blood pressure) and circulating factors (e.g., pro-inflammatory cytokines, proteomics, metabolomics). (Cohort 2)
VI. To explore the biological activity of exercise as evaluated by changes in prostate-specific antigen (PSA) and diffusion-weighted multiparametric magnetic resonance imaging (mpMRI) with dynamic contrast enhancement. (Cohort 3 [active surveillance])
VII. To explore the biological activity of exercise as evaluated by changes in ctDNA, CH, tumor transcriptional and (epi)genomic profile. (Cohort 3 [active surveillance])
VIII. To explore the pharmacodynamics of exercise as evaluated by changes in physiological correlates (e.g., exercise capacity, body weight, blood pressure, heart rate) and circulating factors (e.g., proteomics, metabolomics). (Cohort 3 [active surveillance])
IX. To explore the pharmacodynamics of exercise as evaluated by changes in physiological correlates (e.g., exercise capacity, body weight, blood pressure, heart rate) and circulating factors (e.g., proteomics, metabolomics, ctDNA (as appropriate). (Cohort 4 [Lynch syndrome])
X. To collect fresh frozen mucosal tissue from standard of care surveillance biopsies (at baseline and post intervention) for single cell ribonucleic acid (RNA)-Sequencing. (Cohort 4 [Lynch syndrome])
XI. To examine changes in epithelial cell proliferation (Ki67) and apoptosis (cleaved caspase-3) from baseline to post-intervention. (Cohort 4 [Lynch syndrome])
XII. To examine changes in cfDNA for monitoring and detection of early-stage tumors in patients with Lynch syndrome. (Cohort 4 [Lynch syndrome])
XIII. To evaluate changes in immune cell phenotypes using single-cell phenotyping of peripheral blood. (Cohort 4 [Lynch syndrome])
XIV. To estimate the feasibility of exercise at 24 weeks. (Phase 0a) (Cohort 5 [EDD])
XV. To explore the pharmacodynamics of exercise therapy as evaluated by changes in patient physiology (e.g., exercise capacity, body weight, blood pressure). (Phase 0a) (Cohort 5 [EDD])
XVI. To explore changes in patient-reported outcomes including, but not limited to quality of life and fatigue. (Phase 0a) (Cohort 5 [EDD])
XVII. To evaluate safety. (Phase 0a) (Cohort 5 [EDD])
XVIII. To estimate the feasibility of exercise at 24 weeks. (Phase 0b) (Cohort 5 [EDD])
XIX. To explore the pharmacodynamics of exercise therapy as evaluated by changes in patient physiology (e.g., exercise capacity, body weight, blood pressure). (Phase 0b) (Cohort 5 [EDD])
XX. To explore changes in patient-reported outcomes including, but not limited to quality of life and fatigue. (Phase 0b) (Cohort 5 [EDD])
XXI. To evaluate safety. (Phase 0b) (Cohort 5 [EDD])
OUTLINE: Cohorts 1 and 2 closed to accrual with amendment dated 12/2021. Cohort 3 closed to accrual with amendment dated 02/2024. Cohort 5 added with amendment dated 5/2024. Cohort 4 closed to accrual with amendment dated 08/2024.
Patients receive an electronic tablet device and a kit that includes an activity tracker, heart rate monitor, blood pressure cuff, and scale, and complete an individualized exercise program consisting of walking on a treadmill for 150-300 minutes per week for up to 52 weeks. Patients with prostate cancer undergoing active surveillance may optionally continue exercise intervention for up to 104 weeks. Patients receiving treatment in an EDD protocol complete the exercise program for up to 24 weeks in the absence of disease progression. Patients also undergo collection of blood samples for CH and ctDNA biomarker analysis. Additionally, patients may undergo additional blood sample collection, echocardiography, cardiopulmonary exercise testing, pulmonary function testing, and/or mpMRI throughout the study.
After completion of study, patients are followed up at 2 weeks.
Trial PhaseNo phase specified
Trial Typeprevention
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJessica Scott
- Primary ID19-126
- Secondary IDsNCI-2019-04294
- ClinicalTrials.gov IDNCT03996239