Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer

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.