Radium Ra 223 Dichloride in Reducing Pain in Patients with Symptomatic Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• 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 gonadotropin-releasing hormone (GnRH) agonist in combination with an anti-androgen, must first progress through anti-androgen withdrawal prior to being eligible; the minimum timeframe 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 anti-androgen withdrawal (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
• Eastern Cooperative Oncology Group (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
• White blood cell (WBC) >= 3 x 10^9/L
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Hemoglobin >= 9.0 g/dL
• Creatinine < 1.5 x institutional upper limit of normal (ULN)
• Bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Albumin > 25 g/L
• All acute toxicities as a result of any prior treatment must have resolved to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 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 Health Insurance Portability and Accountability Act (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 to 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 castration-resistant prostate cancer (CRPC) (> 2 lung and/or liver metastases [size >= 2 cm]; 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 computed tomography (CT), magnetic resonance imaging (MRI) or chest X-ray within the 8 weeks prior to registration
• Concurrent chemotherapy; patients may be on other non-chemotherapy anti-cancer treatments, per Food and Drug Association (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 4.0 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