A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Radium-223 dichloride (Xofigo, BAY88-8223); Abiraterone acetate; Prednisone; Enzalutamide
Intervention description: Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus; Abiraterone acetate 1000 mg (4 x 250 mg tablets) taken orally once daily for up to two years following last dose of radium-223 dichloride; Prednisone 5 mg capsule taken orally twice daily for up to two years following last dose of radium-223 dichloride; Enzalutamide 160 mg (four 40 mg capsules) taken orally once daily for up to two years following last dose of radium-223 dichloride
Intervention MeSH terms: Prednisone; Abiraterone Acetate; Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective in this study is to evaluate bone scan response at Week 24 based on the
      quantified technetium-99 bone scan lesion area (BSLA). The safety of radium-223 dichloride in
      combination with abiraterone acetate or enzalutamide will be investigated. The study will
      evaluate radiological progression free survival, overall survival, and skeletal events. This
      study will also explore the clinical utility of different imaging modalities (whole body
      quantified technetium-99 bone scan, DW-MRI [diffusion-weighted magnetic resonance imaging]
      and NaF [sodium fluoride] PET-CT [positron emission tomography-computed tomography] scan) and
      will have a separate central radiological review for applicable secondary and exploratory
      imaging endpoints. All subjects will be randomized as assigned randomly by the IXRS
      (interactive voice / web response system) system in a 1:1:1 ratio into one of the treatment
      arms: radium-223 dichloride alone, 50 kBq/kg (55 kBq/kg after implementation of NIST
      [National Institute of Standards and Technology] update) every 4 weeks for up to 6 doses;
      radium-223 dichloride, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4
      weeks up to 6 doses together with abiraterone acetate 1,000 mg daily and prednisone 5 mg bid
      (twice daily); radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST
      update) every 4 weeks up to 6 doses together with enzalutamide 160 mg daily. The study will
      consist of screening, treatment and follow-up periods. Study will continue until disease
      progression as determined by investigator, or when patient meets criteria for withdrawal from
      study. Subjects in treatment arms with abiraterone/prednisone or enzalutamide will have the
      option to continue taking oral study therapy until the end of the study (2 years from the
      last dose of radium-223 dichloride) if the investigator deems the subject may benefit and
      there is no clinical or radiological progression. Subjects who discontinue all study
      treatment prior to 2 years from last radium-223 dichloride treatment will enter active
      follow-up. During the active follow-up period, the subject will have a safety visit at the
      clinic every 12 weeks from the EOT (end of treatment) for up to 2 years from the last dose of
      radium-223 dichloride. Beyond 2 years from last radium-223 dichloride treatment,subjects will
      enter long-term follow-up and will be followed via phone contact at intervals to assess for
      safety (hematological toxicity and new primary malignancies) and overall survival. A separate
      long-term safety follow-up study protocol is planned. Once implemented, the study subjects
      surviving after the end of the active follow-up will be transitioned to this separate
      long-term safety follow-up protocol.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate

          -  Known castration-resistant disease

          -  Serum PSA ≥2 ng/mL (μg/L)

          -  Multiple skeletal metastases (≥2 hot spots) on bone scan

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.

          -  Life expectancy ≥6 months

          -  Adequate hematologic, hepatic, and renal function

        Exclusion Criteria:

          -  History of visceral metastasis, or visceral metastases

          -  Malignant lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter

          -  Medical condition that would make prednisone (corticosteroid) use contraindicated

          -  Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg
             prednisone bid

          -  Treatment with more than one chemotherapy agent for prostate cancer

          -  Prior systemic radiotherapy and hemibody external radiotherapy

          -  History of pituitary or adrenal dysfunction

          -  Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed
             Paget's disease of bone)

          -  Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy

          -  History of seizures (taking/not taking anticonvulsants), arteriovenous malformation in
             the brain, head trauma with loss of consciousness

          -  Central nervous system (CNS) metastases