Radium-223: evaluation of activity and surrogate response

INTERVENTION: Patients will be randomised to receive either 50kBq/kg or 80kBq/kg of radium 223. Patients in both arms will receive radium‐223 every 4 weeks for up to 6 treatments. Follow up will be from 4 weeks after the last administration of radium‐223. Patients will be evaluated every four months until 1 year after last administration. CONDITION: Prostate cancer ; Cancer PRIMARY OUTCOME: The proportion of patients showing bone metastases response on diffusion weighted MRI (DW‐MRI). From pre‐treatment to any point after 1st injection and the end of cycle 6 will be used to define response. INCLUSION CRITERIA: 1. Histologically or cytologically confirmed adenocarcinoma of the prostate. 2. Known castration resistant disease defined as: 2.1. Castrate serum testosterone level: = 50 ng/dL (2.0nM) 2.2. Bilateral orchidectomy or on maintenance androgen ablation therapy with LHRH agonist or polyestradiol phosphate throughout the study 2.3. Serum PSA progression defined by PCWG II criteria (i.e. two consecutive increases in PSA over a previous reference value, each measurement taken at least 1 week apart) 3. Serum PSA value = 2 ng/mL 4. Available ALP result from a blood sample taken within previous 8 weeks 5. Multiple skeletal metastases (= 2 hot spots) on bone scintigraphy within previous 12 weeks 6. Age =16 years 7. ECOG performance status 0‐2. 8. Life expectancy = 6 months. 9. No prior chemotherapy for CRPC (adjuvant chemotherapy for hormone naïve disease is permissible). 10. Adequate laboratory requirements: 10.1.Absolute neutrophil coun