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A double-blind, dose-response, phase II, multicentre study of radium-223 (Alpharadin TM ) for the palliation of painful bone metastases in hormone refractory prostate cancer patients

Phase 1
Conditions
The target population is patients suffering from bone pain due to skeletal metastasis secondary to prostate cancer.
Registration Number
EUCTR2004-000299-15-SE
Lead Sponsor
Algeta AS
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Male
Target Recruitment
0
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 is currently treated with polyestradiolphosphate to castrate level, 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nilutamide, megestrol acetate, polyestradiolphosphate, aminoglutethimide, and ketoconazole, has been recently added or withdrawn must demonstrate progression of disease and be at least 4 weeks beyond the start or discontinuation of such agents; for bicalutamide 6 weeks is required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 start or discontinuation of flutamide, nilutamide, megestrol acetate, polyestradiolphosphate, aminoglutethimide, and ketoconazole, and at least 6 weeks after start or 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 greater than the second PSA value and > 5 ng/ml
3. Multifocal (>1) skeletal metastases confirmed by bone 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 ³ 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 at least > 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 examination
10. The patient has been fully informed about the study and has signed the informed consent form
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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. Patients 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 non-melanoma 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
11. Patients with imminent or established spinal cord compression based on clinical findings and/or MRI

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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