Assess Gamma H2AX Positivity in Circulating Prostate Cancer Cells Before and After Radium 223

In this pilot study, researchers want to find out if Radium 223 given as part of standard
treatment for prostate cancer can decrease the number of circulating prostate cancer cells.
Radium 223 kills prostate cancer cells by damaging their DNA. Other than looking at the
changes in the number of circulating prostate cancer cells before and after Radium 223,
researchers would also like to look at the changes in a DNA damage marker, called gamma H2AX,
in the circulating prostate cancer cells before and after treatment with Radium 223.
Assessing the DNA damage marker gamma H2AX is investigational. It is performed in the same
tube of blood that is used for assessing the changes in the number of circulating prostate
cancer cells.

Inclusion Criteria:

- Male patients 18 years or older

- Histologically or cytologically confirmed adenocarcinoma of the prostate

- Receiving radium 223 as standard of care for symptomatic metastatic castration
resistant prostate cancer to the bone as documented by bone scan or Sodium Fluoride
positron emission tomography (PET) bone scan.

- No evidence of visceral metastasis

- Prior surgical castration or concurrent use of GnRH analogue (i.e., medical
castration) with testosterone at screening <50 ng/dL.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 -2, ECOG 3 is allowed
if due to pain

- Adequate organ function: Serum alanine aminotransferase (ALT) or aspirate
aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN); Total bilirubin <
1.5 s ULN; Estimated creatinine clearance must be >40 mL/min; Absolute neutrophil
count (ANC) > 1500/l; Hemoglobin above 10 g/dl; platelet count > 100,000/l.

- Stable medical condition, including the absence of acute exacerbations of chronic
illnesses, serious infections or major surgery within 28 days prior to study
enrollment

- Life expectancy of 6 months or more

- Must agree to practice effective barrier contraception during the entire study
treatment period & through for 6 months after the last dose of study drug, or agree to
completely abstain from heterosexual intercourse

- Able to give written informed consent

- Have at least 2 CTCs at baseline

Exclusion Criteria:

- Exposure to radioisotope therapy (samarium 153, strontium 89) within 24 weeks or
exposure to external beam radiation within 12 weeks of receiving the first dose of
Radium 223

- Documented central nervous system metastases, has a history of seizure, stroke or
transient ischemic attack (TIA)

- Treatment with any investigational compound within 30 days prior to the first dose of
study drugs

- Diagnosis or treatment for another systemic malignancy within 2 years before the first
dose of study drugs, or previously diagnosed with another malignancy & have any
evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in
situ of any type are not excluded if they have undergone complete resection.

- New York Association Class III or IV heart failure

- Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
life threatening illness unrelated to cancer, or any serious medical or psychiatric
illness that could, in investigators opinion, potentially interfere with participation
in this study.

- Potential participants with delayed healing of wounds, ulcers, and/or bone fractures

- Inability to comply with protocol requirements