Radium-223 in Biochemically Recurrent Prostate Cancer

• INCLUSION CRITERIA:

• Histopathological confirmation of prostate adenocarcinoma confirmed in either theLaboratory of Pathology at the National Institutes of Health (NIH) Clinical Center,or Walter Reed National Military Medical Center prior to enrollment. If nopathologic specimen is available, participants may enroll with a pathologist sreport showing a histologic diagnosis of prostate cancer and a clinical courseconsistent with the disease.

• Biochemical progression after definitive surgery or radiation define as follows:

• Participants must have a detectable PSA

• Negative CT scan/MRI and Tc99 bone scan for metastatic prostate cancer. (Only Tc99will be used to detect bone lesions, CT/MRI would be used to detect soft tissuelesions)

• Presence of findings on PET scan (i.e., NaF PET scan) suspicious for metastaticprostate cancer in bone. Note: while lymph node findings would be allowed andprovide the opportunity for the assessment of any abscopal effects, PET scanfindings suggesting visceral disease will be excluded.

• Testosterone >= 100 ng/dL

• ECOG performance status of 0 1

• Recovery from acute toxicity related to prior therapy, including surgery andradiation, (defined as no toxicity >= grade 2).

• Hematological eligibility parameters (within 16 days before treatment initiation):

• Granulocyte count >= 3,000/mm^3

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Hgb >= 10 g/dL

• Hepatic function eligibility parameters (within 16 days before treatment initiation)

-- Bilirubin <=1.5 mg/dL (OR in participants with Gilbert s syndrome, a totalbilirubin <= 3.0), AST and ALT <= 2.5 times upper limit of normal.

• Adequate renal function defined by eGFR within normal as predicted by the CKD-EPIequation (>= 50 mL/min/1.73m^2) or by measure o f creatinine clearance from 24-hoururine collection.

• No other active malignancies within 36 months of treatment initiation (with theexception of nonmelanoma skin cancers or carcinoma in situ of the bladder)

• Participants must be >=18 years old. Currently, no dosing or adverse event data isavailable on the use of radium in participants < 18 years of age; therefore, onlyadults are included in this study.

• Ability of subject to understand and the willingness to sign a written informedconsent document.

• The effects radium-223 on the developing human fetus are unknown but based on themechanism of action, radium-223 has the potential to cause fetal harm. For thisreason, men must agree to use condoms for the duration of study therapy and at least 6 months

after the last treatment administration. Female partners of reproductive potential must use a highly effective method of birth control during treatment and for 6 months after their partner s last treatment administration. Should a woman become pregnant or suspect she

is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

EXCLUSION CRITERIA:

• Participants with immunocompromised status due to Human Immunodeficiency Virus (HIV)infection or other immunodeficiency diseases because this is a trial with a primaryendpoint looking at immune response, requiring functional immune systems.

• Participants who test positive for HBV or HCV.

• Chronic administration (defined as daily or every other day for continued use > 14days) of systemic corticosteroids within 28 days of treatment initiation. Use ofcorticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasalsprays, intraarticular, and topical agents) is allowed.

• Receipt of any organ transplantation, including allogeneic stem-celltransplantation, but with the exception of transplants that do not requireimmunosuppression (e.g. corneal transplant, hair transplant).

• Serious intercurrent medical illness that, in the judgement of the investigator,would interfere with participant's ability to carry out the treatment program.

• Subjects required other medications known to alter PSA including 5-alpha reductaseinhibitors (finasteride and dutasteride) and alternative therapies (e.g.,phytoestrogens and saw palmetto).

• History of prior chemotherapy.

• History of prior systemic therapy with radionuclides (e.g., strontium-89,samarium-153, rhenium-186, rhenium-188, or radium 223 dichloride).

• Receipt of an investigational agent within 28 days (or 56 days for an antibody-basedtherapy) of treatment initiation.

• Major surgery within 28 days prior to treatment initiation.

• PET scan findings suggesting visceral disease.