Radium Ra 223 Dichloride and Enzalutamide in Treating Patients with Metastatic Prostate Cancer That Is Resistant to Antihormone Therapy

Inclusion Criteria

• Histologically documented adenocarcinoma of the prostate
• Life expectancy of >= 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 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 magnetic resonance imaging (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 castrated levels of serum testosterone (< 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 disease defined by the following criteria: * PSA: increasing PSA levels as defined by the Prostate Cancer Clinical Trials Working Group (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 >= 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: >= 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and PCWG2 criteria * Non-measurable disease: ** Lymph node disease: 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
• White blood cell (WBC) >= 3,000 cells/uL
• Absolute neutrophil count (ANC) >= 1,500 cells/uL
• Platelet count >= 100,000 cells/uL
• Hemoglobin (HgB) >= 10.0 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Creatinine =< 1.5 X ULN
• Aspartate aminotransaminase (AST, serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
• Alanine aminotransaminase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• Albumin > 25 g/L
• Creatinine clearance > 30 ml/min
• Transfusion of blood products are not allowed to normalize blood parameters within 4 weeks of the first radium treatment
• Men must agree to use adequate contraception beginning at the signing of the informed consent (ICF) until at least 6 months after the last dose of study drug; 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 Health Insurance Portability and Accountability Act (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 bisphosphonates or denosumab are allowed
• Prior cytotoxic chemotherapy with the exception of docetaxel or cabazitaxel; treatment with docetaxel or cabazitaxel must be discontinued >= 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 or imminent pathologic long-bone fracture (cortical erosion on radiography > 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, 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 grade >= 2 infection as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) (i.e. alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9) (phenytoin, warfarin), and cytochrome P450 family 2, subfamily C, polypeptide 19 (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 > 100.5°F or 38.1°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 >= 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