Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis

Inclusion Criteria:

Eligible subjects will conform to all of the inclusion criteria listed below:

1. Subject must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
2. Subject is willing and able to comply with the protocol, including all study visits and procedures.
3. Subject is a male, greater than 18 years at time of enrollment.
4. Life expectancy of at least 9 months.
5. Subject has histologically documented prostate cancer confirmed by a pathology report from a prostate biopsy or radical prostatectomy specimen.
6. Subject must:

   • have initiated a stable dose of daily Abiraterone Acetate plus Prednisone within 90 days of enrollment, or

   • plans to initiate a stable daily dose of Abiraterone plus Prednisone within 30 days of the first Radium Ra 223 dichloride treatment.
7. Subject must plan to receive all 6 Radium Ra 223 dichloride injections and daily oral doses of Abiraterone plus Prednisone during the trial, per protocol.
8. Subject has a history of bone metastasis from prostate cancer as evidenced by imaging performed within 90 days of enrollment from one of the following:

   • Tc Bone Scan or

   • Sodium Fluoride PET/CT Scan

   \*If a bone scan is used, solitary lesions which could be contributed to causes other than prostate cancer must be confirmed with a second modality (i.e.: plain films, CT Scan or MRI.
9. Subject has Castrate Resistant Prostate Cancer, defined as rising PSA with a testosterone level \</= 50ng/dl (2.0 nM/L) while receiving androgen deprivation therapy (medical or surgical castration).

   \* PSA progression will be defined as at least 2 rising PSA levels taken at least 7 days apart with the 2nd PSA being 2.0 ng/dl or greater.
10. Subject has the presence of bone pain requiring treatment with:

1\) EBRT within the previous 12 weeks prior to enrollment, or 2) Analgesic medications (including but not limited to acetaminophen, NSAIDS, Cox-2 inhibitors, and narcotic Opioids).

11\. Subject has an ECOG performance status of 0-2 at screening 12. Acceptable hematology and serum biochemistry screening values:

• White Blood Cell (WBC) \>/= 3,000/mm3

* Absolute Neutrophil Count (ANC) \>1500/mm3
* Platelet (PLT) count \>100,000/mm3
* Hemoglobin (HGB) \> 10.0 g/dL (100g/L; 6.2 mmol/L
* Creatinine \<1.5 ULN
* Total bilirubin level \<1.5 X ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 X ULN
* albumin \>25 g/L
* Baseline electrolytes within normal limits ( Sodium, potassium, chloride, calcium, phosphate, magnesium, LDH, γGT, urea, total protein) 13. Normal Liver Function Tests (LFT) and normal Renal Function Tests (RFT) at screening visit. If the subject has LFT's or RFT's greater than 2.5 times the upper limit of normal (ULN), Medical Monitor review, in conjunction with the subject's PI, will be required.

  14\. Subjects receiving Anti-Resorptive medications (such as Zolendronic Acid or denosumab) must be on a stable dose for at least 90 days prior to enrollment (Cycle 1/Week 1/ Day 1). Anti-resorptive medications may be added to the subject's regimen after the End of Treatment visit has been completed. Anti-resorptive medication withdrawal will be allowed per Investigator discretion due to adverse events attributable to that medication.

  15\. Subjects of childbearing potential must agree to use adequate contraception beginning at the enrollment until at least 30 days after the last dose of the study drugs. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.

Exclusion Criteria:

Eligible subjects must not meet any of the exclusion criteria listed below:

1. Subject has known malignant pleural effusion, or known lung, liver or brain metastasis (lymph node only metastasis \< 6 cm in short-axis diameter is allowed).
2. Subject has a history of visceral metastatic disease as assessed by abdominal/pelvic CT or chest x-ray within the previous 8 weeks.
3. Subject has received previous treatment with Abiraterone Acetate for longer than 90 days prior to enrollment, or any prior treatment with Radium Ra 223 dichloride.
4. Subject has a known medical contraindication to Prednisone, Abiraterone Acetate or Radium Ra 223 dichloride.
5. Subject is not willing to initiate a stable dose of daily Abiraterone Acetate plus Prednisone within 90 days of enrollment, or does not plan to initiate a stable daily dose of Abiraterone Acetate plus Prednisone within 30 days of the first Radium Ra 223 dichloride treatment.
6. Subject does not plan to receive all 6 infusions of Radium Ra 223 Dichloride and daily Abiraterone Acetate plus Prednisone during the trial, per protocol.
7. Subject has received previous strontium-89, samarium-153, rhenium-186, or rhenium-188 for the treatment of bone metastasis within 24 weeks prior to enrollment.
8. Subject has received denosumab or Zolendronic Acid for less than 90 days prior to enrollment, or if the subject plans to discontinue an anti-resorptive medication prior to the EOT visit.
9. Subject has received an investigational product or experimental therapy within 4 weeks of enrollment, or if initiation of either is planned prior to the EOT visit.
10. Subject has had treatment with cytotoxic chemotherapy within the previous 4 weeks, or planned prior to the End of Treatment visit, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks prior to enrollment (persistent myelosuppression, GI toxicity, or severe fatigue (ongoing neuropathy is not exclusionary).
11. Subject has a history of any medical condition that may be compromised by an increase in blood pressure, or severe liver insufficiency (r Child-Pugh class B or C).
12. Subject has a history of a myocardial infarction or cardiac arrhythmia within 6 months prior to enrollment.
13. Subject has a history of previous radiotherapy \>25% of bone marrow, including hemibody radiation.
14. Subject has a history of any other malignancy within the previous 5 years. A history of squamous or basal cell carcinoma or low-grade superficial bladder cancer that has been adequately treated at least 12 months prior to enrollment is not exclusionary.
15. Subject has undergone major surgery within 4 weeks prior to enrollment.
16. Subject has had a blood transfusion or erythropoietin stimulation agents within 4 weeks of enrollment.
17. Subject has known imminent or established spinal cord compression.
18. Subject has a serious concurrent medical condition or psychiatric illness.
19. Subject has a history of other serious illness of medical condition including, but not limited to any uncontrolled infection, congestive heart failure New York Heart Association (NYHA) class III or IV, Crohn's Disease or Ulcerative Colitis, uncontrolled hypertension or Bone Marrow Dysplasia at screening.
20. Subject has any condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures.
21. Subject is not able to swallow the study treatment capsules.
22. Subject has unmanageable fecal incontinence.
23. Subject has a history of any size pelvic lymphadenopathy if it is thought to be a contributor to current hydronephrosis.