A Placebo-controlled Phase II Study of Bone-targeted Radium-223 in Symptomatic Hormone-refractory Prostate Cancer

Inclusion Criteria:

1. Histologically/cytologically confirmed adenocarcinoma of the prostate
2. Patient has received or is receiving hormonal treatment (orchiectomy, polyoestradiol phosphate, or gonadotropin-releasing hormone analogue with or without antiandrogen)
3. Metastatic disease with positive bone scan within 2 months before treatment with more than one cancer related lesion or with one painful cancer related lesion in the presence of increasing PSA levels as follows: PSA >5 ng/ml, with increases on at least 2 successive occasions at least 2 weeks apart.
4. Patient is referred to local field radiotherapy (EBR) for metastatic bone pain. The area to be treated (index site) should match the positive bone scan, local radiation area not exceeding 400 cm2
5. ECOG performance status: 0-2
6. Life expectancy: at least 3 months
7. Age more than 40 years

8. Laboratory requirements:

   1. Hematology: Neutrophil count ≥1,5 x 109/L Platelet count at least ≥100 x109/L and stable Hemoglobin >100 g/l or 10 g/dL
   2. Hepatic function: Bilirubin within normal institutional limits ASAT and ALAT <2,5 times upper limit of normal (ULN)
   3. Renal function: Creatinine <1,5 times the ULN (i.e. NCI grade ≤1)
9. Patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examinations
10. Patient has been fully informed about the study and has signed the informed consent form

Exclusion Criteria:

1. Has received an investigational drug in the 4 weeks before or is scheduled to receiving one during the planned treatment period
2. Has received chemo-, immunotherapy or external radiotherapy within weeks before study drug administration
3. Has started treatment with bisphosphonates within 3 months before administration of study drug.
4. Has previously received systemic radiotherapy with strontium, samarium or rhenium
5. Change in hormonal therapy within the last 6 weeks before study drug administration
6. Other currently active (relapse within the last 3 year) malignancy (except nonmelanoma skin cancer) or known brain, liver, lung, visceral and lymphatic metastases dominating the clinical picture of the patient
7. Has received blood transfusion within last month

8. Other serious illness or medical condition as follows:

   1. any uncontrolled infection
   2. heart insufficiency, grade 3 or 4 as specified in NCI-CTC criteria
   3. grade 2 or greater motor or sensory neuropathy
   4. Crohn's disease or Ulcerative colitis 9) Known non-pathological bone fracture within the last two months