Clinical trial NCT00667199 (phase 2, status: completed)
Conditions: hormone refractory prostate cancer, bone metastases
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: radium-223 dichloride (bay88-8223)
SMILES: Cl[223Ra]Cl
Eligibility criteria:

        Inclusion criteria:

          -  Histologically/cytologically confirmed adenocarcinoma of the prostate

          -  Patient is hormone refractory with evidence of progressive disease:

               -  Patient must be maintained on androgen ablation therapy with LHRH agonist or have
                  undergone orchiectomy

               -  Patient's testosterone level is required to be equal to or below 50 ng/dl

               -  Patients in which flutamide, nilutamide, megestrol acetate, polyestradiol
                  phosphate, aminoglutethimide, and ketoconazole, has been recently withdrawn must
                  demonstrate progression of disease and be at last 4 weeks beyond the
                  discontinuation of such agents; for bicalutamide 6 weeks is required

               -  Increase in PSA levels in two consecutive measurements with at least one week
                  apart, demonstrating an increase over the reference (nadir) value, and with the
                  final PSA >/= 5 ng/ml

                    -  A reference PSA (nadir) value must be measured at least 4 weeks after the
                       discontinuation of flutamide, nilutamide, megestrol acetate, polyestradiol
                       phosphate, aminoglutethimide, and ketoconazole, and at least 6 weeks after
                       discontinuation of bicalutamide

                    -  If the third PSA value is lower than the second value, the patient could
                       still be eligible, provided a fourth measurement obtained at least 1 week
                       after the third PSA value, is grater than the second PSA value and >/= 5
                       ng/ml

          -  Multifocal (>1) skeletal metastases confirmed by bone scintigraphy within 6 weeks

          -  Bone pain with a score of at least 2 on BPI average pain, despite adequate use of
             analgesics, that correlates with areas of increased uptake (osteoblastic activity) on
             bone scintigraphy

          -  Performance status: ECOG 0-2 or Karnofsky >/= 60%

          -  Life expectancy: At least 3 months

          -  Age more than 40 years

          -  Laboratory requirements:

               -  Neutrophil count >/= 1,5 x 109/L

               -  Platelet count >/= 100 x109/L

               -  Hemoglobin > 95 g/L

               -  Bilirubin within normal institutional limits

               -  ASAT and ALAT <2,5 times upper limit of normal (ULN)

          -  The patient is willing and able to comply with the protocol (including maintenance of
             patient diary, completion of pain assessment forms), and agrees to return to the
             hospital for follow-up visits and examinations

          -  The patient has been fully informed about the study and has signed the informed
             consent form

        Exclusion criteria

          -  Has received an investigational drug within 4 weeks before the administration of
             radium-223, or is scheduled to receiving one during the study period

          -  Has received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks
             prior to entering the study, or those who have not recovered from adverse events due
             to agents administered more than 4 weeks earlier

          -  Has received prior hemibody external radiotherapy

          -  Has received systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or
             rhenium 188 for the treatment of bony metastases within the last year prior to
             inclusion

          -  Has started treatment with bisphosphonates less than 3 months prior to administration
             of study drug

          -  Patients experiencing hormone withdrawal syndrome, or are </= 4 weeks post withdrawal
             of antiandrogen therapy (6 weeks for bicalutamide)

          -  Patients who have started steroids or changed to treatment with steroids within the
             last 4 weeks prior to administration of radium-223

          -  Has other clinically significant or symptomatic disease, which might interfere with
             the assessment of bone pain, e.g. spinal cord compression, compression or infiltration
             of a neural plexus, nerve root or peripheral nerves

          -  Other currently active (relapse within the last 3 year) malignancy (except
             non-melanoma skin cancer), or known brain or visceral metastases dominating the
             clinical picture of the patient

          -  Other serious illness or medical condition:

               -  any uncontrolled infection

               -  cardiac failure Classification III or IV (New York Heart Association)

               -  Crohn disease or Ulcerative colitis

               -  known bone fracture within 8 weeks