Patient case: 70-year-old male with prostate cancer; genetic feature: PTEN

Clinical trial: 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

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.

Detailed description: This study is a phase III multinational, multicenter,randomized, double blind, placebo controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus prednisone/prednisolone).The study period will consist of screening/randomization, treatment, active follow-up with clinic visits, active follow-up without clinic visits, and long-term follow-up phases. In this study, subjects will receive study treatment (radium-223 dichloride or placebo in addition to abiraterone acetate plus prednisone/prednisolone for the first 6 cycles followed by abiraterone acetate plus prednisone/prednisolone thereafter) until an on-study symptomatic skeletal event (SSE) occurs (or other withdrawal criteria are met). Follow-up will continue for up to 7 years or until the subject dies, is lost to followup, or withdraws informed consent and actively objects to collection of further data.This study will be conducted at approximately 150 investigative study centers and approximately 800 subjects will be enrolled.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed adenocarcinoma of the prostate
  -  Male subjects of age ≥ 18 years
  -  Prostate cancer progression documented by prostate specific antigen 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(prostate specific antigen) progression after discontinuing the anti-androgen prior to enrollment.
  -  Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L).
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status 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 bid.
  -  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.

Relevance to patient case: not relevant