Standard Dose Versus High Dose and Versus Extended Standard Dose Radium-223 Dichloride in Castration-resistant Prostate Cancer Metastatic to the Bone
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Radium-223 dichloride (Xofigo, BAY88-8223)
Intervention MeSH terms: Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 391.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will assess different doses and regimens of radium-223 dichloride on the incidence
      of symptomatic skeletal events. Eligible subjects must have castration resistant prostate
      cancer with 2 or more skeletal metastases documented within 8 weeks of randomization.
      Subjects will be randomized to one of 3 treatment arms in a 1:1:1 fashion: a standard regimen
      of radium-223 dichloride of 50 kBq/kg (55 kBq/kg after implementation of NIST update)
      injections every month for 6 months, a high dose regimen of 80 kBq/kg (88 kBq/kg after
      implementation of NIST update)injections every month for 6 months or an extended duration
      regimen of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month
      for 12 months. Following the treatment phase, subjects will be followed up every 12 weeks for
      a minimum of 2 years, at which point they will enter a long term follow-up period during
      which they are seen every 6 months for up to 7 years after the last dose of radium
      dichloride. Symptomatic skeletal event and safety endpoints will be assessed at each clinic
      visit. Pain and analgesic use data will be collected every 4 weeks through Week 48.
      Additionally, radiological assessments including MRI/CT of the abdomen and pelvis and chest
      CT, as well as technetium-99 bone scans will be performed at Weeks 8, 16, and 24 and continue
      every 12 weeks thereafter until disease progression is documented in either the bone or in
      soft tissue. Radiological imaging will be evaluated by blinded central review.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate

          -  Castration-resistant disease defined as:

               -  Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)

               -  Bilateral orchiectomy or maintenance on androgen ablation therapy with
                  luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or
                  polyestradiol phosphate

               -  Serum PSA (Prostate specific antigen) progression defined as 2 subsequent
                  increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR

               -  Radiographic evidence of disease progression in bone (according to Prostate
                  Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA
                  progression

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of
             ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.

          -  Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of
             randomization

        Exclusion Criteria:

          -  History of visceral metastasis, or visceral metastases

          -  Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter

          -  Central nervous system (CNS) metastases

          -  Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks
             prior to randomization, or planned treatment with cytotoxic chemotherapy agents for
             prostate cancer during the treatment period or follow-up

          -  Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed
             Paget's disease of bone)

          -  Prior treatment with radium-223 dichloride

          -  Prior systemic radiotherapy and hemibody external radiotherapy