Aerobic Training in Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This study is being done to examine the safety and feasibility of a supervised progressive exercise program in women diagnosed with metastatic breast cancer. Previous research among women with metastatic breast cancer has shown that some of the treatments commonly used in this population may have an adverse impact on physical fitness levels leading to feelings of fatigue and poor quality of life. Supervised exercise training has been shown to reduce some of these side-effects in women with early-stage breast cancer receiving common cancer treatments. However, it is not known if supervised exercise training is a safe and feasible intervention in women with metastatic breast cancer. This study is designed to find out if supervised exercise training is safe as the patients undergo treatments for metastatic breast cancer.

Official Title
-----------------
Phase II Trial of Aerobic Training in Metastatic Breast Cancer

Conditions
-----------------
Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Behavioral: Progressive Stretching Group
* Behavioral: Nonlinear Aerobic Training
* Other: Blood draw
* Other: Cardiopulmonary Exercise Testing (CPET)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: MSK histologically confirmed metastatic breast cancer Measurable disease (or nonmeasurable bone-only disease) assessed by CT or PET/CT performed as part of standard of care, at the discretion of the attending oncologist in the Breast Medicine Service ≥18 years of age; Life expectancy >3 months; ECOG ≤ 1 Sedentary, as per the leisure score index (LSI) of the Godin Leisure-Time Exercise Questionnaire (GLTEQ) . Participants who perform regular moderate or vigorous intensity exercise at least 5 days/week, for at least 30 minutes/session, are not eligible 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 Normal cardiac function (left ventricular ejection fraction ≥50%); Medical clearance from attending oncologist indicating no relative contraindications to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention; Patients with treated and stable brain lesions of a duration of ≥ 2 months may be enrolled Willing to be randomized to one of the study arms Female Exclusion Criteria: Any of the following absolute contraindications to cardiopulmonary exercise testing: 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 Suspected dissecting aneurysm Uncontrolled asthma Pulmonary edema Room air desaturation at rest ≤ 85% Respiratory failure Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis) Mental impairment leading to inability to cooperate. Any other condition or intercurrent illness that, in the opinion of the investigator, makes the participant a poor candidate for the trial Presence of extensive skeletal metastases, defined as more than five (5) sites of bony disease, or any symptomatic site of disease in the spine, hip, or femur. Note that, patients with more than five bony sites may be deemed eligible at the discretion of the attending oncologist.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Progressive Stretching Group<br> | Behavioral: Progressive Stretching Group<br>* Participants assigned to the progressive stretching group will be provided with a progressive stretching program that matches the aerobic training interventions in terms of program length (16 weeks), social interaction (all sessions will be supervised), and session duration (20-45 minutes/session, ± 10 minutes).<br>Other: Blood draw<br>* At Weeks 4, and 8, all participants will have a complete blood count (CBC) test performed.<br>|
| Experimental: Nonlinear Aerobic Training<br> | Behavioral: Nonlinear Aerobic Training<br>* Participants assigned to the nonlinear aerobic training arm will perform no more than 150 minutes per week of structured supervised aerobic training as part of clinical trial participation. Exercise performed outside the structured sessions (i.e., contamination) will be assessed via self-report of exercise behavior using the Godin-Leisure Time Exercise Questionnaire (GLTEQ). For ethical reasons, we will not instruct participants not to exercise outside the structured sessions, but we we will encourage participants to maintain their level of exercise behavior prior to study initiation.<br>Other: Blood draw<br>* At Weeks 4, and 8, all participants will have a complete blood count (CBC) test performed.<br>Other: Cardiopulmonary Exercise Testing (CPET)<br>* At the end of Week 6, participants repeat the CPET in the nonlinear aerobic training group.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of aerobic training | Safety will be evaluated by the type and prevalence of adverse events during study-related assessments as well as aerobic training and progressive stretching sessions. The NCI Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE) will be used to grade toxicities during the trial. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility of aerobic training | feasibility will be evaluated by examining several different end points including rates of study eligibility and accrual, etc; however, sample size calculations are based on an integration of aerobic training attendance rate (in the aerobic training group) as well as global trial attrition rates. Together, these end points will be used to determine overall study feasibility. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stretching, Nonlinear Aerobic Training, 14-170