A Study to Test Radium-223 With Docetaxel in Patients With Prostate Cancer

Inclusion Criteria:

• Willing and able to provide written informed consent (ICF) and HIPAA authorizationfor the release of personal health information. A signed informed consent must beobtained before screening procedures are performed.

NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

• Males 18 years of age and above

• Histological or cytological proof of prostate cancer

• Documented progressive mCRPC based on at least one of the following criteria:

1. PSA progression defined as 25% increase over baseline value with an increase inthe absolute value of at least 1.0 ng/mL that is confirmed by another PSA levelwith a minimum of a 1 week interval and a minimum PSA of 1.0 ng/mL.

2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the LD ofall target lesions based on the smallest sum LD since treatment started or theappearance of one or more new lesions.

3. Progression of bone disease (evaluable disease) or two or more new bone lesionsby bone scan.

• Two or more bone lesions

• ECOG 0- 1

• Normal organ function with acceptable initial laboratory values within 14 days ofrandomization:

• Albumin > 30 g/L

• ANC ≥ 1.5 x 10^9/L

• Hemoglobin ≥ 10 g/dL

• Platelet count ≥ 100 x 10^9/L

• Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN)

• Bilirubin ≤ ULN (unless documented Gilbert's disease)

• SGOT (AST) ≤ 1.5 x ULN

• SGPT (ALT) ≤ 1.5 x ULN

• WBC count ≥ 3 x 10^9/L

• Subjects must agree to use a medically acceptable method of birth control (e.g.,spermicide in conjunction with a barrier such as a condom) or sexual abstinence forthe duration of the study, including 30 days after the last dose of study drug.Sperm donation is prohibited during the study and for 30 days after the last dose ofstudy drug. Female partners must use hormonal or barrier contraception unlesspostmenopausal or abstinent.

• Serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivationwith an LHRH analogue (agonist or antagonist) if they have not undergoneorchiectomy.

• All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less.

• Willing and able to comply with the protocol, including follow-up visits andexaminations

Exclusion Criteria:

• Received any other investigational therapeutic agents or other anticancer therapieswithin 4 weeks prior to randomization.

°Note: If this requirement to have a washout of 2 weeks or 5 half-lives prior torandomization causes potential treatment delay due to Radium-223 importationtimelines, the PCCTC must be contacted at pcctc@mskcc.org to request approval torandomize the subject prior to the completion of the washout. Requests for earlyrandomization must be accompanied by written assurance by the site that the washoutwill be completed prior to treatment start.

• Received external beam radiotherapy within the 4 weeks prior to randomization.

° Note: If prolonging randomization to complete EBRT washout causes potentialtreatment delay due to Radium-223 importation timelines, the PCCTC must be contactedat pcctc@mskcc.org to request approval to randomize the subject prior to thecompletion of the washout. Requests for early randomization must be accompanied bywritten assurance by the site that the washout will be completed prior to treatmentstart.

• Has an immediate need for external beam radiotherapy.

• Has received any systemic bone-seeking radiopharmaceutical in the past.

• Has received any prostate cancer directed chemotherapy in the castration resistantsetting. Subjects who have received up to 6 prior doses of docetaxel in thecastration sensitive setting are permitted if they have not experienced diseaseprogression within 36 weeks of last treatment with docetaxel.

• Has received four or more systemic anticancer regimens for mCRPC.

• Treatment with docetaxel or abiraterone for non-castrate metastatic disease ispermissible and does not count towards the lines of therapy for mCRPC

• A 'line' is a regimen. Combinations of hormones and other types of therapiescount as single lines.

• Has known Grade ≥3 docetaxel-related toxicities or docetaxel toxicity related doseinterruption or discontinuation.

• Has received blood transfusions or growth factors within the last 4 weeks prior torandomization.

• Symptomatic nodal disease (i.e., scrotal, penile, or leg edema).

• Has visceral metastases with ≥ 3 lung and/or liver metastases or individual lesion ≥2 cm, as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8weeks prior to randomization.

• Symptomatic loco-regional disease that causes ongoing Grade 3 or Grade 4 urinary orrectal symptoms.

• Subjects with a "currently active" second malignancy other than non-melanoma skincancers or non-invasive bladder cancers or other in-situ or non-invasivemalignancies. Subjects are not considered to have a "currently active" malignancy ifthey have completed therapy and are free of disease for ≥ 3 years.

• Has imminent or established cord compression based on clinical findings and/or MRI.

• Known bone marrow dysplasia

• Has received any of the following in the 4 weeks prior to randomization: 5-alpha-reductase inhibitors, herbal medications, natural hormonally active foods (e.g., phytoestrogens) or other food supplements known to alter PSA in humans

• Any other serious illness or medical condition that would, in the opinion of theinvestigator, make this protocol unreasonably hazardous, including but not limitedto:

• Uncontrolled infection

• NYHA III or IV heart failure

• Crohn's disease or those with ulcerative colitis who have not undergone acolectomy

• Known active infection with HIV, Hepatitis B or Hepatitis C