Study of Aerobic Training for People Receiving Chemotherapy for Breast Cancer

Study Overview
=================
Brief Summary
-----------------
In this study, investigators will compare standard Aerobic Training/AT with adaptive Aerobic Training/AT. Standard AT will be a fixed (unchanging) amount of walking each week, while adaptive AT will adjust the level of exercise depending on participants' response to the exercise. Investigators will see how both study approaches (standard AT and adaptive AT) affect participants' CRF.

Official Title
-----------------
Phase 2 Trial of Adaptive Versus Standard Dosing of Aerobic Training in Patients Receiving Chemotherapy for Primary Breast Cance

Conditions
-----------------
Breast Cancer, Breast Carcinoma

Intervention / Treatment
-----------------
* Behavioral: Adaptive Aerobic Training/AT Dosing
* Behavioral: Standard (fixed) Aerobic Training/AT dosing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥18 years Female Diagnosed with primary breast cancer as defined by one of the following: Histological confirmation As per standard of care imaging Scheduled to receive neoadjuvant/adjuvant chemotherapy Performing ≤90 minutes of moderate- and/or strenuous-intensity exercise per week, as evaluated by self-report Willingness to comply with all study-related procedures Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria: Achieving a plateau in oxygen consumption, concurrent with an increase in power output; A respiratory exchange ratio ≥ 1.10; Attainment of maximal predicted heart rate (HRmax) (i.e., within 10 bpm of age-predicted HRmax [HRmax = 220-Age[years]); Volitional exhaustion, as measured by a rating of perceived exertion (RPE) ≥ 18 on the BORG scale. Exclusion Criteria: Enrollment onto any other interventional investigational study, except interventions determined by the PI not to confound study outcomes Receiving treatment for any other diagnosis of invasive cancer Distant metastatic malignancy of any kind Mental impairment leading to inability to cooperate Any of the following contraindications to cardiopulmonary exercise testing: i. Acute myocardial infarction within 3-5 days of any planned study procedures; ii. Unstable angina; iii. Uncontrolled arrhythmia causing symptoms or hemodynamic compromise; iv. Recurrent syncope; v. Active endocarditis; vi. Acute myocarditis or pericarditis; vii. Symptomatic severe aortic stenosis; viii. Uncontrolled heart failure; ix. Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures; x. Thrombosis of lower extremities; xi. Suspected dissecting aneurysm; xii. Uncontrolled asthma; xiii. Pulmonary edema; xiv. Respiratory failure; xv. Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis) xvi. Room air desaturation at rest ≤ 85% 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adaptive Aerobic Training/AT Dosing<br>Participants with newly diagnosed primary breast cancer initiating chemotherapy. | Behavioral: Adaptive Aerobic Training/AT Dosing<br>* o In Phase A ( 32 weeks), AT will consist of supervised walking delivered up to 7 days per week using an adaptive dosing schedule that starts at 90 min/wk and is escalated 30 min/wk every 2 weeks to a maximal dose of 300 mins/wk. In Phase B ( 20 weeks), AT will consist of supervised adaptive AT dosing in patients with a CRF Δ<3.50 ml O2 .kg-1.min-1 from baseline to  32 weeks, or unsupervised AT in patients with a CRF Δ>3.50 ml O2 .kg-1.min-1 from baseline to  32 weeks. Supervised AT will be monitored using TeleEx.<br>|
| Active Comparator: Standard (fixed) Aerobic Training/AT dosing<br>Participants with newly diagnosed primary breast cancer initiating chemotherapy. | Behavioral: Standard (fixed) Aerobic Training/AT dosing<br>* In Phase A ( 32 weeks), AT will consist of supervised walking delivered up to 7 days per week to achieve a cumulative total duration of: 90 min/wk (standard fixed dosing). In Phase B ( 20 weeks), AT will consist of supervised adaptive AT dosing in patients with a CRF Δ<3.50 ml O2 .kg-1.min-1 from baseline to  32 weeks, or unsupervised AT in patients with a CRF Δ>3.50 ml O2 .kg-1.min-1 from baseline to  32 weeks. Supervised AT will be monitored using TeleEx.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory fitness (CRF) response rate | The primary endpoint will be CRF response rate as assessed by the proportion of patients with a peak oxygen consumption (VO2peak; ml O2 .kg-1.min-1 ) change from baseline (T0) to T2 ( 32 weeks) of ≥3.50 ml O2 .kg-1.min-1 . A CRF change ≥3.50 ml O2 .kg-1.min-1 will be considered a response; a change <3.50 ml O2 .kg-1.min-1 will be considered a non-response. | 32 weeks from baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Breast carcinoma, Primary breast cancer, Aerobic Training, 22-364, Memorial Sloan Kettering Cancer Center