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.