Hormone refractory prostate cancer with skeletal metastases MedDRA version: 14.1 Level: PT Classification code 10027452 Term: Metastases to bone System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Alpharadin
Product Code: Radium-223
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Radium-223 chloride
CAS Number: 444811-40-9
Current Sponsor code: Radium-223
Other de
Sponsors
Algeta ASA
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the prostate 2. Known hormone refractory disease defined as: • Castrate serum testosterone level: = 50 ng/dL (1.7 nmol/ L) • Bilateral orchiectomy or maintenance on androgen ablation therapy with LHRH agonist or polyestradiol phosphate throughout the study • Serum PSA progression defined as two consecutive increases in PSA over a previous reference value, each measurement at least 1 week apart) 3. Serum PSA value = 5 ng/mL (µg/L) 4. Multiple skeletal metastases (= 2 hot spots) on bone scintigraphy within previous 12 weeks 5. No intention to use cytotoxic chemotherapy within the next 6 months 6. Either regular (not occasional) analgesic medication use for cancer related bone pain or treatment with EBRT for bone pain within previous 12 weeks 7. Age = 18 years 8. ECOG Performance status (PS): 0-2 9. Life expectancy = 6 months 10. Laboratory requirements: a. Absolute neutrophil count (ANC) = 1.5 x 10^9/L b. Platelet count = 100 x10^9/ L c. Hemoglobin = 10.0 g/dL (100 g/L; 6.2 mmol/L) d. Total bilirubin level = 1.5 institutional upper limit of normal (ULN) e. ASAT and ALAT = 2.5 ULN f. Creatinine = 1.5 ULN g. Albumin > 25 g/L 11. Willing and able to comply with the protocol, including follow-up visits and examinations 12. Must be fully informed about the study and signed the informed consent form Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 225 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 675
Exclusion criteria
Exclusion criteria: 1. Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period 2. Eligible for first course of docetaxel, i.e. patients who are fit enough, willing and where docetaxel is available 3. Treatment with cytotoxic chemotherapy within previous 4 weeks, or planned during the treatment period, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks ago 4. Prior hemibody external radiotherapy 5. Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks 6. Prior treatment with radium-223 7. Blood transfusion or erythropoetin stimulating agents within previous 4 weeks 8. Other malignancy treated within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer) 9. History of visceral metastasis, or visceral metastases as assessed by abdominal/pelvic CT or chest x-ray within previous 8 weeks 10. Malignant lymphadenopathy exceeding 3 cm in short-axis diameter 11. Imminent or established spinal cord compression based on clinical findings and/or MRI 12. Any other serious illness or medical condition such as, but not limited to: • any uncontrolled infection • cardiac failure NYHA III or IV • Crohns' disease or Ulcerative colitis • Bone marrow dysplasia 13. Unmanageable faecal incontinence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare, in patients with symptomatic HRPC and skeletal metastases, the efficacy of best standard of care plus Alpharadin versus best standard of care plus placebo, with the primary efficacy endpoint being overall survival (OS). ;Secondary Objective: Main - Time to total-ALP progression - Total ALP response - Time to occurrence of first skeletal related event - Total ALP normalisation - Time to PSA progression Other -Time to occurrence of first use of external beam radiotherapy to relieve skeletal symptoms -Time to occurrence of first use of radio-isotopes to relieve skeletal symptoms - Time to occurrence of first new symptomatic pathological bone fractures (vertebral and non-vertebral) - Time to occurrence of first tumour related orthopaedic surgical intervention - Time to occurrence of first spinal cord compression - Time to occurrence of first start of any other anti-cancer treatment - Time to occurrence of first deterioration of ECOG PS by at least two points from baseline [includes death (score of 5), by definition] - Changes in PSA - Changes in total-ALP;Primary end point(s): Overall survival: time from date of randomisation to the date of death;Timepoint(s) of evaluation of this end point: Patients will be evaluated every 2 months until 1 year from first administration, and thereafter every 4 months until 3 years from first administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to total-ALP progression - Total ALP response - Time to occurrence of first skeletal related event - Total ALP normalisation - Time to PSA progression;Timepoint(s) of evaluation of this end point: • Time to total-ALP progression i. in patients with no total-ALP decline from baseline (at least 12 weeks from baseline) ii. in patients with an initial total-ALP decline from baseline (confirmed by a second value obtained three or more weeks later). • Total-ALP response (approximately 4 or more weeks later). • Time to occurrence of first skeletal related event (throughout the study). • Total-ALP normalisation (return of total-ALP value to within normal range at 12 weeks in 2 consecutive measurements, at least 2 weeks apart). • Time to PSA progression i. in patients with no PSA decline from baseline (at least 12 weeks from baseline) ii. in patients with an initial PSA decline from baseline (confirmed by a second value obtained three or more weeks later). | — |
Countries
Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Hong Kong, Israel, Italy, Netherlands, Norway, Poland, Singapore, Slovakia, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Algeta ASA
Outcome results
None listed