E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone refractory prostate cancer with skeletal metastases |
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E.1.1.1 | Medical condition in easily understood language |
Prostate cancer which has spread to bone |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027452 |
E.1.2 | Term | Metastases to bone |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
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). |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Substudy for Clinical Evaluation of QTc Interval Prolongation in a Subgroup of the Patient Population
Date: 25 January 2010
Objective: The aim of the BC1-06 ECG substudy is to obtain more information of any clinically relevant effect of Alpharadin on QTc prolongation and proarrhythmic potential. |
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E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival: time from date of randomisation to the date of death |
|
E.5.1.1 | 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. |
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E.5.2 | 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
|
|
E.5.2.1 | 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). |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Hong Kong |
India |
Israel |
Italy |
Netherlands |
Norway |
Poland |
Singapore |
Slovakia |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |