Trial Information

Phase II Trial of Aerobic Training in Metastatic Breast Cancer

Primary To determine the feasibility and safety of supervised aerobic training in women
receiving endocrine therapy, chemotherapy, and/or radiotherapy for metastatic breast cancer

Secondary

- To explore the potential effect (means and variation) on treatment toxicity, patient
symptoms, and functional capacity, relative to attention control (i.e., mock exercise)

- To explore the potential effect (means and variation) on biomarkers associated with
metastatic breast cancer prognosis (i.e., inflammatory cytokines and growth factors),
relative to attention control

Primary: Safety and feasibility evaluated by assessing the rates of study eligibility,
overall accrual, attrition, and exercise adherence. Safety will be evaluated by the type and
prevalence of adverse events during study-related assessments and aerobic training sessions.
Tracking and monitoring of exercise-related adverse events will be assessed using the
following methods: (1) stringent monitoring and recording (in the patient case report form;
case report form, this will include a detailed past medical history, complete blood count
panel history from first line chemotherapy, and detailed medication information) of
physiologic outcomes and vital signs (e.g., heart rate, blood pressure, etc.) prior to,
during, and following every intervention session, and (2) at the beginning of each week, the
exercise physiologist will spend the first 10 minutes of every session discussing any
potential negative side-effects of the intervention assignment and any injuries that may
have occurred. Discussions will include topics such as sleep, depression, diet, exercise,
and any other related topics that should come up. All events will be recorded in the
patient CRF, (3) every two weeks all patients will complete the Common Terminology Criteria
for Adverse Events (CTCAE) v4.0 questionnaire. The CTCAE, developed by the NCI, tracks
treatment toxicity and adverse events applicable to all oncology clinical trials regardless
of chronicity or modality, (4) every three months a meeting of all investigators will be
scheduled to review and discuss all reported non-serious and serious adverse events for
early identification of negative issues and development of solutions. All serious adverse
events will be immediately reported to Duke Institutional Review Board and immediately
circulated to all study investigators for appropriate discussion, and (5) early stopping
rules in response to a differential higher frequency of adverse events in a particular study
group (Risk outweighs benefit as determined by primary investigator and oncologist).

Secondary:

1. Treatment toxicity and complete blood count panel will be assessed after every
chemotherapy cycle or every month if on hormone or radiation therapy according to the
CTCAE v.4.0 as described above.

2. Insulin sensitivity as assessed by an oral glucose tolerance test,

3. Exercise capacity as measured by a symptom-limited cardiopulmonary exercise test,

4. Pulmonary function as assessed by hand held spirometry,

5. Cardiac function as assessed by echocardiography at rest and exercise,

6. Neurocognitive function (a computerized neurocognitive test battery called Central
Nervous System Vital Signs including verbal memory test, visual memory test, finger
tapping test, symbol digit coding, Stroop test, shifting attention test, continuous
performance test, four part continuous performance test).

7. Autonomic function as assessed by beat-to-beat heart, blood pressure, and
cerebrovascular blood flow velocity via transcranial Doppler.

8. Patient-reported outcomes will be determined using standardized and validated
questionnaires to assess quality of life, fatigue, and other common patient symptoms.

9. Systemic Cytokines / Angiogenic Factors assessed in fasted blood and prepared for
multiplex assay analysis using Luminex 100/200 System (Luminex Corp, Austin, Tx;
http://www.luminexcorp.com/products/luminex_200.html).