The purpose of this study is to find out if Radium-223 is effective in reducing cancer pain within 12 weeks of treatment. In order to see if Radium-223 is effective, the patient's level of pain will be followed throughout the study.

Inclusion Criteria:

• Males aged 18 years of age and above

• Histological or cytological proof of prostate adenocarcinoma

• Castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)

• Patients who have experienced disease progression despite initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through anti- androgen withdrawal prior to being eligible. The minimum time frame to document failure of anti-androgen withdrawal will be four weeks. Patients on second-line (or beyond) hormonal maneuvers, and patients who had no PSA decline on combined androgen blockade as first line therapy, need not progress through AAW in order to be eligible.

• Known progressive castration-resistant disease, defined as:

  • Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first treatment, each measurement at least one week apart. Serum PSA at screening ≥ 2 ng/mL or
  • Documented appearance of new lesions by bone scintigraphy

• ECOG Performance Status of 0-2 2 or more bone metastases demonstrated on bone scintigraphy

• Pain at baseline as measured by a BPI worst pain score average of ≥ 3. The BPI worst pain score average will be based on the worst pain scores completed by the patient in the 7 consecutive pretreatment days. A minimum of 4 days of pain scores must be completed by the patient in the 7 day window in order to calculate the average worst pain score. The investigator will optimize the subject's pain regimen prior to study entry.

• Normal organ function with acceptable initial laboratory values:

  • WBC ≥ 3 x 109 /L
  • ANC ≥ 1.5 x 109 /L
  • Platelets ≥ 100 x 109 /L
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine < 1.5 x institutional upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 x ULN
  • AST/ALT ≤ 2.5 x ULN
  • Albumin > 25 g/L

• All acute toxicities as a result of any prior treatment must have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF) [Note: Ongoing grade 2 neuropathy as a result of treatment with a cytotoxic chemotherapy regimen is permitted]

• Life expectancy of at least 6 months

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information NOTE: HIPAA authorization may be either included in the informed consent or obtained separately

• Willing and able to comply with the protocol, including follow-up visits, examinations as well as having the ability to self-report pain and fatigue using a Patient Reported Outcome (PRO) instrument

• Willingness to use adequate methods of contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug

Exclusion Criteria:

• Prior exposure to Radium-223

• Received an investigational therapy within the 4 weeks prior to registration or is scheduled to receive one during the treatment period

• Received a new anti-cancer agent within 4 weeks prior to registration

• Received external beam radiotherapy within 4 weeks prior registration

• Received systemic therapy with radionuclides (e.g. strontium-89, samarium-153, rhenium-186 or rhenium-188) for the treatment of bone metastases

• Treatment with cytotoxic chemotherapy within 4 weeks prior to registration

• Symptomatic nodal disease, i.e. scrotal, penile or leg edema. Visceral metastases (including cerebral metastases) from CRPC (>2 lung and/or liver metastases [size ≥2cm]; Lymphadenopathy exceeding 6 cm in short-axis diameter or any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis), as assessed by CT, MRI or chest X-ray within the 8 weeks prior registration.

• Concurrent chemotherapy. Patients may be on other non-chemotherapy anti-cancer treatments, per FDA labeling of Radium-223, provided that these are not changed during the primary pain assessment period Major surgery within 30 days prior to registration.

• Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.

• Patients with a, "currently active," second malignancy other than non-melanoma skin cancers or non-invasive bladder cancers or other in-situ or non-invasive malignancies. Patients who have completed therapy for a prior malignancy and are free of disease for ≥3 years are eligible.

• Any other serious illness or medical condition, such as but not limited to:

  • Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2
  • Cardiac failure New York Heart Association (NYHA) III or IV
  • Crohn's disease or ulcerative colitis
  • Bone marrow dysplasia
  • Fecal incontinence

• Any other condition which, in the opinion of the Investigator, would make the subject unsuitable for trial participation

• NOTE: Any patient found to be ineligible prior to treatment initiation will require re-screening.