Radium-223 in Patients With Hormone Refractory Prostate Cancer (HRPC) and Skeletal Metastases

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate.

2. Hormone refractory with evidence of rising PSA:

   • Patient must be maintained on androgen ablation therapy with LHRH agonist (stable dose for at least 8 weeks prior to study entry), or have undergone bilateral orchiectomy
   • Serum testosterone level is required to be </=50 ng/dl

   • Patients who have received prior antiandrogen drug therapy:

     • Flutamide, nilutamide or cyproterone acetate must have stopped at least four weeks prior to study drug administration and progression, as defined by rising PSA as defined below, must have been demonstrated since cessation;
     • Bicalutamide must have stopped at least six weeks prior to study drug administration and progression, as defined by rising PSA as defined below, must have been demonstrated since cessation

   • PSA progression

     • Progressive rise in PSA, defined as two consecutive increases in PSA documented over a previous reference value (measure 1). The first increase in PSA (measure 2) should occur at a minimum of 1 week from the reference value (measure 1). This increase in PSA should be confirmed (measure 3) after a minimum of 1 week. If the confirmatory PSA value (measure 3) is less than the previous value, the patient will still be eligible provided the next PSA measure (measure 4) is found to be greater than the second PSA value (measure 2).
3. Skeletal metastases confirmed by bone scintigraphy within the last 6 weeks
4. Performance status: ECOG 0-2
5. Life expectancy: >/= 6 months

6. Laboratory requirements:

   • Neutrophil count >/= 1.5 x 109/L
   • Platelet count >/= 100 x109/L
   • Haemoglobin >/= 95 g/L
   • Total bilirubin level within normal institutional limits
   • ASAT and ALAT </= 2,5 times upper institutional limit of the normal range
   • S-Creatinine </= 1,5 times upper institutional limit of the normal range
7. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
8. Able and willing to give written informed consent.

Exclusion Criteria:

1. Has received an investigational drug within 4 weeks prior to the administration of radium-223, or is scheduled to receive one during the treatment and post-treatment period
2. Has received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks prior to administration of study drug, or has not recovered from adverse events due to agents administered more than 4 weeks earlier
3. More than one regimen of previous cytotoxic chemotherapy
4. Has received prior hemibody external radiotherapy
5. Has a need for immediate external radiotherapy
6. Has received systemic radiotherapy with radium-223, strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within the last year prior to administration of study drug.
7. Has started treatment with bisphosphonates less than 3 months prior to administration of study drug. Patients are allowed to be on bisphosphonates provided patient is on a stable dose for >/= 12 weeks before administration of study drug.
8. Patients who are </= 4 weeks (6 weeks for bicalutamide) post withdrawal of antiandrogen therapy
9. Patients who have started or stopped systemic steroids, within a week prior to study drug administration, or are expected to be subject to changes in the systemic steroid medication
10. Other currently active (relapse within the last 3 years) malignancy (except non-melanoma skin cancer) that are not prostate cancer metastases
11. Visceral (e.g. liver, lung) metastases from prostate cancer as assessed by abdominal/ pelvic CT or chest radiograph within six weeks before administration of study drug;
12. Lymph node metastases with short-axis diameter greater than 2 cm.
13. Bulky loco-regional disease

14. Any other serious illness or medical condition, for example:

    • any uncontrolled infection
    • any patient who has clinical heart failure severe enough to cause marked limitation of activity, and who is only comfortable at rest; or any patient who has heart failure more severe than this (NYHA Heart Failure Class III or IV).
    • Crohns disease or ulcerative colitis