A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

Inclusion Criteria:

Male age ≥ 18 years.
Histologically or cytologically confirmed adenocarcinoma of the prostate. Life expectancy of at least 6 months.
ECOG performance status of zero, one, or two.
Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).

Symptomatic as defined by either of the following:

(a) Regular use of analgesic medication for cancer-related bone pain (≥ level 1; WHO ladder for cancer pain), or
(b) Treatment with EBRT for bone pain (though EBRT must be completed ≥12 weeks prior to enrollment in this trial).
Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment.
Subjects must be able to understand and be willing to sign the written informed consent form.
All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
No intention to use cytotoxic chemotherapy within the next 6 months. Subjects must agree to use adequate contraception beginning at the signing of the ICF until at least 6 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator.

Acceptable hematology and serum biochemistry screening values:

White Blood Cell Count (WBC) ≥ 3,000/mm3
Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
Platelet (PLT) count ≥ 100,000/mm3
Hemoglobin (HGB) ≥10 g/dl (Please note: it is acceptable from the standpoint of study eligibility to undergo transfusion in order to achieve hemoglobin ≥ 10 g/dl)
Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Creatinine ≤ 1.5 x ULN
Albumin > 25 g/L
Willing and able to comply with the protocol, including follow-up visits and examinations.

Exclusion Criteria:

Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted).
Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up.
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.
Received previous radiotherapy to approximately >25% of bone marrow.
Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer).
Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality.
Presence of brain metastases.
Lymphadenopathy exceeding 6 cm in short-axis diameter.
Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
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, 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
Known bone marrow dysplasia
Fecal incontinence.
Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.