Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Radium-223 dichloride (Xofigo, BAY88-8223); Matching placebo (normal saline); Abiraterone; Prednisone/Prednisolone
Intervention description: 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of NIST update) body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles; Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles; 1000 mg once daily, oral, with best supportive care; 5 mg twice daily, oral, with best supportive care
Intervention MeSH terms: Prednisone; Prednisolone; Radium Ra 223 dichloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 806.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase III; Radium-223 dichloride; Abiraterone acetate; Combination therapy; Chemotherapy-naive; Bone metastasis; Castration-resistant prostate cancer (CRPC)

Summary:

      To determine if the addition of radium-223 dichloride to standard treatment is able to
      prolong life and to delay events specific for prostate cancer which has spread to the bone,
      such as painful fractures or bone pain which needs to be treated with an X-ray machine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate

          -  Male subjects of age ≥ 18 years

          -  Prostate cancer progression documented by prostate specific antigen (PSA) according to
             the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression
             according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1

          -  Two or more bone metastases on bone scan within 4 weeks prior to randomization with no
             lung, liver, other visceral and/or brain metastasis

          -  Asymptomatic or mildly symptomatic prostate cancer

          -  Subjects who received combined androgen blockade with an anti-androgen must have shown
             PSA progression after discontinuing the anti-androgen prior to enrollment

          -  Maintenance of medical castration or surgical castration with testosterone less than
             50 ng/dL (1.7nmol/L)

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) score 0 or 1

        Exclusion Criteria:

          -  Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes,
             mitoxantrone and estramustine

          -  Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg
             prednisone/prednisolone twice daily

          -  Pathological finding consistent with small cell carcinoma of the prostate

          -  History of visceral metastasis, or presence of visceral metastasis detected by
             screening imaging examinations

          -  History of or known brain metastasis

          -  Malignant lymphadenopathy exceeding 3 cm in short-axis diameter

          -  Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and
             during the whole screening period before randomization

          -  Imminent spinal cord compression based on clinical findings and/or magnetic resonance
             imaging (MRI). Subjects with history of spinal cord compression should have completely
             recovered

          -  Use of opiate analgesics for cancer-related pain, including codeine and
             dextropropoxyphene, currently or anytime during the 4- week period prior to
             randomization.