Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer

Inclusion Criteria: * Histologically documented adenocarcinoma of the prostate. * Men at least 18 years of age and life expectancy of greater than or equal to 6 months. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * Metastatic disease as evidenced by both lymphadenopathy and bony metastases or just bony metastases on baseline bone scan and/or computed tomography (CT) scan or MRI of the abdomen and pelvis within 28 days of registration. Chest imaging is only required if clinically indicated or if there is known disease in the chest. * Castration resistant prostatic adenocarcinoma. Subjects must have castrate levels of serum testosterone (less than 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy. * Previously received docetaxel or are not healthy enough per clinical judgment or declined to receive it * Evidence of disease progression on or after the most recent systemic treatment defined by the following criteria: * Prostate-Specific Antigen (PSA): Increasing serum PSA levels as defined by the Prostate Cancer Working Group 2 (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value). If the third measurement is below the second, then a fourth measurement must be greater than the second. The confirming third or fourth measurement must be greater or equal to 2 ng/mL. PSA progression must have occurred within 15 months of registration (with at least 7 days between each PSA measurement). Additionally, the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer. * Measurable disease: greater than or equal to 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by RECIST 1.1 and PCWG2 criteria. * Non-measurable disease: * Lymph node disease: The appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. * Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. * Symptomatic bone metastases * Adequate hematologic, renal, and liver function as evidenced by laboratory test results. (Transfusion of blood products are not allowed to normalize blood parameters within 4 weeks of the first radium treatment.) * Subjects who have previously received docetaxel or are ineligible for docetaxel and who are candidates for treatment with enzalutamide alone or enzalutamide in combination with Radium-223 * Men must agree to use adequate contraception beginning at the signing of the Informed Consent Form until at least 6 months after the last dose of study drug. Because of the potential side effect on spermatogenesis associated with radiation, men who are sexually active must agree to use condoms and their female partners of reproductive potential must agree to use a highly effective contraceptive method during and for 6 months after completing treatment. * Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines to ensure compliance with HIPAA regulations. Exclusion Criteria: * The presence of known brain metastases, malignant pleural effusions, or malignant ascites. Brain MRI is required at screening only if clinically indicated. * Visceral metastases as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality) * Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases * Prior treatment with enzalutamide. * Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than the protocol based treatment. LHRH agonist or antagonist therapy, and supportive non-cancer directed therapies like bisphosphonates or denosumab are allowed. * Prior cytoxic chemotherapy with the exception of docetaxel or cabazitaxel. Treatment with docetaxel or cabazitaxel must be discontinued greater than 4 weeks from the time of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however, ongoing neuropathy is permitted). * Major surgery within 30 days prior to start of study drug * Current, untreated pathologic long-bone fractures, imminent pathologic long-bone fractures (cortical erosion on radiography greater than 50%). * Prior hemi-body external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count (ANC), and platelets. * Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior to screening * Lymphadenopathy exceeding 3 cm in short-axis diameter * Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis. * Current or imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression. * Any other serious illness or medical condition in the opinion of the investigator, such as but not limited to: * Any greater than or equal to Grade 2 infection as defined by NCI-CTCAE version 4.03. * Cardiac failure New York Heart Association (NYHA) III or IV * Crohn's disease or ulcerative colitis * Bone marrow dysplasia * Fecal incontinence * Concomitant use of narrow therapeutic index drugs that are metabolized by CYP3A4 (i.e. alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (phenytoin, warfarin), and CYP2C19 (S-mephenytoin). \[Note: Patients on stable doses of anti-coagulation with warfarin and fentanyl will be eligible, as long as they are monitored closely with additional international normalized ratio (INR) monitoring\]. * Any infection requiring parenteral antibiotic therapy or causing fever (temperature greater than 100.5 degrees F or 38.1 degrees C) within 1 week prior to registration. * Concurrent other malignancy with the exception of: a) cutaneous squamous cell and basal carcinomas, b) adequately treated stage 1-2 malignancy , c) adequately treated stage 3-4 malignancy that had been in remission for greater than or equal to 2 years at the time of registration. * Inability to comply with the protocol and/or not willing or not available for follow-up assessments * Any medical intervention or other condition which, in the opinion of the Principal Investigator could compromise adherence with study requirements or otherwise compromise the study's objectives