EXTEND Exercise Trial

Inclusion Criteria

• •1. Male age ≥ 18 years.
• •2. Histologically-confirmed adenocarcinoma of the prostate.
• •3. Completion of appropriate prior treatment with local therapy (i.e., prostatectomy, radiation therapy or equivalent), per NCCN Guidelines.
• •4. Detectable PSA, defined as PSA ≥0.01 ng/ml
• •5. Appropriate for treatment with ADT in the opinion of the treating physician.
• •6. Serum total testosterone ≥150 ng/dL (5.2 nmol/L).
• •7. ECOG performance status of ≤ 1 (Appendix A)
• •8. Planned treatment with castration therapy (GnRH agonist/antagonist) for ≥8 months.
• •9. 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 \<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.
• •10. Able to swallow enzalutamide and comply with study requirements.
• •11. Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 9), defined as at least one of the following:
• •* Achieving a plateau in oxygen consumption concurrent with an increase in power output;
• •* Respiratory exchange ratio ≥ 1.1 (RER);
• •* Volitional exhaustion with a rating of perceived exertion ≥ 17 (RPE)
• •12. Must be able to complete an acceptable muscular strength test (assessed using calculated one-repetition maximum (1-RM)) at baseline (see Section 9), in the opinion of the fitness specialist, exercise physiologist, or trained designee administering the test.
• •13. Life expectancy of ≥ 12 months.
• •14. Must use a condom if having sex with a pregnant woman.
• •15. Male subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:
• •* Condom (barrier method of contraception); AND
• •One of the following is required:
• •* Established use of oral, or injected or implanted hormonal method of contraception by the female partner;
• •* Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner;
• •* Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
• •* Tubal ligation in the female partner;
• •* Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months
• •16. Subjects must have normal organ and marrow function as defined below:
• •* absolute neutrophil count \>1,500/µL
• •* platelets \>100,000/µL
• •* total bilirubin \<2.5 X institutional upper limit of normal
• •* AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
• •* Creatinine ≤ 2.0 OR creatinine clearance \>30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.