E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with painful bone metastases secondary to prostate carcinoma. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to investigate whether there is a dose-response relationship for radium-223 in patients with painful bone metastases secondary to prostate carcinoma regarding the palliation of bone pain. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to find the most efficient dose with an acceptable safety profile. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Histologically/cytologically confirmed adenocarcinoma of the prostate 2) 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nilutamide, megestrol acetate, polyestradiolphosphate, aminoglutethimide, and ketoconazole, has been recently withdrawn must demonstrate progression of disease and be at last 4 weeks beyond the discontinuation of such agents; for bicalutamide 6 weeks is required • Increase in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 o A reference PSA (nadir) value must be measured at least 4 weeks after the discontinuation of flutamide, nilutamide, megestrol acetate, polyestradiolphosphate, aminoglutethimide, and ketoconazole, and at least 6 weeks after discontinuation of bicalutamide o 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 3) Multifocal (>1) skeletal metastases confirmed by scintigraphy within the last 6 weeks 4) 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 5) Performance status: ECOG 0-2 or Karnofsky 60% 6) Life expectancy: At least 3 months 7) Age: more than 40 years 8) Laboratory requirements: a. Neutrophil count 1,5 x 109/L b. Platelet count 100 x109/L c. Hemoglobin > 95 g/L d. Bilirubin within normal institutional limits e. ASAT and ALAT <2,5 times upper limit of normal (ULN) 9) The patient is willing and able to comply with the protocol (including maintenance of patient diary and completion of pain assessment forms), and agrees to return to the hospital for follow-up visits and examinations 10) The patient has been fully informed about the study and has signed the informed consent form |
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E.4 | Principal exclusion criteria |
1) Has received an investigational drug within 4 weeks before the administration of radium-223, or is scheduled to receiving one during the study period 2) 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 3) Has received prior hemibody external radiotherapy 4) 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 5) Has started treatment with bisphosphonates less than 3 months prior to administration of study drug 6) Patients experiencing hormone withdrawal syndrome, or are 4 weeks post withdrawal of antiandrogen therapy (6 weeks for bicalutamide) 7) Patient who have started steroids or changed to treatment with steroids within the last 4 weeks prior to administration of radium-223 8) 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 9) Other currently active (relapse within the last 3 year) malignancy (except nonmelanoma skin cancer), or known brain or visceral metastases dominating the clinical picture of the patient 10) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Pain Assessment; the patient’s self assessment of his “average pain over the last 24 hours” using a100 mm Visual Analogue Scale where 0 is “no pain” and 100 is “pain as bad as you can imagine” 2) Analgesic consumption |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The subjects in the trial will be evaluated for palliation of pain for 16 weeks after the administration of the study drug, and the scheduled visit at week 16 is defined as end of study visit. However, long-term follow-up of the patients is justified to obtain survival data and monitor for possible chronic radiation toxicity. The patients will be contacted for possible visits at 6, 9, 12, 18, and 24 months following the administration. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |