LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer

Inclusion Criteria

• Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy. [Late induction permitted within 3 months of starting LHRH analogue therapy or antiandrogen]
• All patients who have not initiated hormone therapy (Early induction patients) must have elevated PSA ≥ 4 ng/ml within 28 days prior to registration. For late induction registrations, PSA must be ≥ 4 ng/ml prior to start of androgen deprivation therapy; either antiandrogen or LHRH analogue or GNRH antagonist .If patients are on antiandrogen, this will need to be discontinued for at least 7 days prior to registration.
• Patients with a history of prior neoadjuvant or adjuvant hormone therapy are eligible provided they have received twenty four or less months of hormone treatment (single or combination treatment, excluding orchiectomy). Both therapies (neoadjuvant/adjuvant hormone therapy) must have been discontinued at least 6 months prior to registration. This is intended to exclude patients who might have been rendered indirectly androgen insensitive.
• There must be no plans to receive concomitant chemotherapy, biological response modifiers, radiation therapy or hormonal therapy. Concomitant radiation therapy is allowed for the palliation of severe pain/neuropathic compression. Prior or concomitant use of megestrol acetate for the treatment of hot flashes is allowed.
• Patients must have a performance status of 0 - 2 by Zubrod Criteria.
• Patients must have recovered from any major infections and/or surgical procedures and,in the opinion of the investigator, not have significant active medical illness precluding protocol treatment or survival.
• No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, superficial or in situ cancer of the bladder. For an invasive cancer the patients should be disease free for at least 3 years prior to enrollment on study.
• For all patients a bone scan must be performed within 60 days prior to registration for tumor assessment. CT scans (abdomen and pelvis) and chest x-ray are optional, but must be repeated if used for disease assessment. For late induction registrations, tumor assessment imaging showing metastatic disease must be available prior to start of androgen deprivation therapy.
• Age 18 or older and willing and able to provide informed consent.
• Willingness to swallow pills and no medical condition that would interfere with this.
• Male patient 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. Patients are also required to use a condom if having sex with a pregnant woman.
• Patient should agree to a tumor tissue biopsy prior to protocol enrollment. Post therapy biopsy is optional.
• Patients who are being treated with a GNRH antagonist should be willing to switch to a LHRH analogue after registration.
• Patients must have one of the following a) Low volume disease (defined as no visceral metastases and 2.5 times the upper limit of normal
• Creatinine > 177 μmol/L (2 mg/dL)
• Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure (NYHA) class 3 or 4 in the past, unless screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is greater or equal to 45%; History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes); History of Mobitz II second degree or third degree heart block without a permanent pacema