EXTEND Exercise Trial

Inclusion Criteria

• Male age ≥ 18 years.
• Histologically-confirmed adenocarcinoma of the prostate.
• Completion of appropriate prior treatment with local therapy (i.e., prostatectomy, radiation therapy or equivalent), per NCCN Guidelines.
• Detectable PSA, defined as PSA ≥0.01 ng/ml
• Appropriate for treatment with ADT in the opinion of the treating physician.
• Serum total testosterone ≥150 ng/dL (5.2 nmol/L).
• ECOG performance status of ≤ 1 (Appendix A)
• Planned treatment with castration therapy (GnRH agonist/antagonist) for ≥8 months.
• Must not have any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training as determined by the attending oncologist:

Absolute Contraindications

• 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 (within 3 months) pulmonary embolus or pulmonary infarction
• Thrombosis of lower extremities
• Suspected dissecting aneurysm
• Uncontrolled asthma
• Pulmonary edema
• Room air desaturation at rest 1,500/µL
• platelets >100,000/µL
• total bilirubin 30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.

Exclusion Criteria

• Definite evidence of metastatic prostate cancer, in the opinion of the treating physician. Pelvic and retroperitoneal lymph nodes < 2.0 cm in short axis are allowed.
• Subjects who have had treatments with GnRH agonists/antagonists and/or anti-androgens within 1 year of randomization.
• Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA values (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of day 29 visit (start of Enzalutamide and ADT).
• Subjects who have had radiotherapy within 12 weeks prior to entering the study or those who have not recovered from adverse events due to agents or therapies administered for treatment of prostate cancer more than 4 weeks earlier (except urinary, rectal, and sexual side effects related to prostatectomy or radiotherapy are permitted)
• Subjects who have had any surgical procedure (i.e. TURP, etc.) within 4 weeks prior to entering the study.
• Subjects who are receiving any other investigational agents.
• Significant cardiovascular disease, including:
• Symptomatic left ventricular dysfunction or known baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of < lower limit of institutional normal (LLN). "Symptomatic" is defined as New York Heart Association (NYHA) Class II or greater. Note: MUGA and ECHCO do NOT need to be measured to establish eligibility for this study.
• Uncontrolled hypertension (in the opinion of the treating provider).
• Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) within 12 months of first dose of study drug.
• Uncontrolled cardiac arrhythmias.
• Coronary or peripheral artery bypass graft within 6 months of first dose of study drug.
• History of CVA, TIA, or rest claudication within 6 months of first dose of study drug.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (in the opinion of the treating provider).
• Subjects with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorptio