['adenocarcinoma of the prostate', 'hormone-resistant prostate cancer', 'recurrent prostate cancer', 'stage iv prostate cancer']
['enzalutamide', 'abiraterone', 'prednisone']

        Eligibility Criteria:

          1. Documentation of Disease - Progressive castration-resistant metastatic prostate cancer
             with histologically or cytologically confirmed adenocarcinoma of the prostate without
             neuroendocrine differentiation or small cell features

          2. Patients must have measurable or non-measurable disease:

               1. Measurable Disease - For visceral or extra nodal lesions to be considered
                  measurable, they must be ≥ 10 mm in one dimension, using spiral CT. For lymph
                  nodes to be considered measurable (ie, target or evaluable lesions), they must be
                  ≥ 20 mm in at least one dimension, using spiral CT.

               2. Non-Measurable Disease - All other lesions, including small lesions (longest
                  diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and
                  truly non-measurable lesions. Lesions that are considered non-measurable include
                  bone lesions (only).

               3. Patients with node only disease (ie, no presence of visceral, extra nodal lesions
                  or bone lesions) must have node(s) that measure ≥ 15 mm in short axis.

          3. Progressive Disease - Patients must have progressive disease at study entry defined as
             one or more of the following three criteria that occurred while the patient was on
             androgen deprivation therapy. For patients enrolling on the basis of soft tissue or
             bone progression, the baseline scan must show progression relative to a comparison
             scan. If the comparison scan is not available, the baseline scan report must reference
             the previous scan to document progression.

               1. PSA progression defined by a minimum of two rising PSA levels with an interval of
                  ≥ 1 week between each determination. Patients who received an anti-androgen must
                  have progression documented by a minimum of two rising PSA levels with an
                  interval of ≥ 1 week between each determination such that at least the second of
                  these rises is ≥ 4 weeks since last flutamide, bicalutamide or nilutamide.

                  The PSA value at the screening should be ≥ 2 µg/L (2 ng/mL) .

               2. Soft tissue disease progression defined by the protocol

               3. Bone disease progression defined by the Prostate Cancer Working Group 2 (PCWG2)
                  with two or more new lesions on bone scan

          4. Prior Treatment

               1. No treatment with prior taxane-based chemotherapy for metastatic disease

                    -  Patients who received prior taxane-based chemotherapy as neoadjuvant or
                       adjuvant therapy for local disease, or who received taxane-based therapy in
                       the PSA clinical (non-metastatic) state is allowable provided that the total
                       duration of exposure was six cycles or less and chemotherapy was completed
                       more than 6 months prior to registration

                    -  Taxane-based chemotherapy that was aborted due to allergic reactions or
                       intolerance to chemotherapy and therefore received one cycle of prior
                       therapy is allowable

               2. No prior enzalutamide, abiraterone or other novel antiandrogen or androgen
                  synthesis inhibitor

               3. No treatment with any of the following for prostate cancer within 4 weeks prior
                  to enrollment:

                    -  Hormonal therapy (e.g., androgen receptor [AR] antagonists, 5 alpha
                       reductase inhibitors, estrogens) Note: Treatment with bicalutamide and
                       nilutamide within 4 weeks prior to enrollment is not allowed. Treatment with
                       flutamide within 4 weeks prior to enrollment is not allowed. Treatment with
                       all other gonadotropin- releasing hormone (GnRH) analogues or antagonists is
                       allowed.

                    -  Chemotherapy

                    -  Biologic therapy

                    -  Investigational therapy

                    -  Immunotherapy

               4. No use of herbal products that may decrease PSA levels within 4 weeks prior to
                  enrollment

               5. No use of systemic steroids greater than the equivalent of 10 mg of
                  prednisone/prednisolone per day within 4 weeks prior to enrollment

               6. No prior use of ketoconazole for greater than 7 days

               7. No prior radiation therapy or radionuclide therapy for the treatment of
                  metastasis within four weeks prior to enrollment

               8. Patients receiving bisphosphonate therapy or denosumab must have been on a stable
                  dose for at least 4 weeks prior to enrollment

               9. Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue,
                  antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)

          5. Patient History

               1. No known or suspected brain metastases (NOTE: patients with treated epidural
                  disease are allowed)

               2. No planned palliative procedures for alleviation of bone pain such as radiation
                  therapy or surgery

               3. No structurally unstable bone lesions suggesting impending fracture

               4. No history of seizure or any condition that may increase the patient's seizure
                  risk (e.g., prior cortical stroke, significant brain trauma). No history of
                  transient ischemic attack (TIA) within 12 months of enrollment

               5. No clinically significant cardiovascular disease including:

                    -  Myocardial infarction (MI) within 6 months

                    -  Uncontrolled angina within 3 months

                    -  Congestive heart failure (CHF) with New York Heart Association (NYHA) class
                       3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening
                       echocardiogram (echo) or multigated acquisition scan (MUGA) performed within
                       three months demonstrates an ejection fraction (EF) > 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 pacemaker in place

                    -  Hypotension (systolic blood pressure [BP] < 86 mmHg) or bradycardia (< 50
                       bpm) at screening

                    -  Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg
                       at screening)

               6. No gastrointestinal (GI) disorder that negatively affects absorption

               7. No major surgery within 4 weeks prior to enrollment

          6. Age and performance status

               1. Age ≥ 18 years of age

               2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

               3. Asymptomatic or mildly symptomatic from prostate cancer

          7. Required Initial Laboratory Values

               1. Granulocytes ≥ 1,500/µL

               2. Platelet count ≥ 100,000/µL

               3. Hemoglobin ≥ 9 g/dL

               4. Creatinine ≤ 2 x upper limits of normal (ULN)

               5. Bilirubin ≤ 1.5 x ULN

               6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 x ULN

               7. Albumin ≥ 3 g/dl

               8. Total testosterone ≤ 50 ng/dL (1.7 nmol/L)
      