E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prolonging bone metastasis-free survival in men with hormone-refractory androgen independent prostate cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
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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 the treatment effect of denosumab with placebo on prolonging bone metastasis-free survival in men with hormone refractory androgen independent prostate cancer who have no bone metastasis at baseline. |
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E.2.2 | Secondary objectives of the trial |
To compare the treatment effect of denosumab with placebo on time to first bone metastasis excluding deaths -overall survival To assess the safety and tolerability of denosumab compared with placebo. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria men with histologically confirmed prostate cancer age .18 years Eastern Cooperative Oncology Group ECOG performance status of 0 or 1 chemical or surgical castration defined as - bilateral orchiectomy also referred to as orchidectomy at least 6 months before randomization, OR - continuous androgen deprivation therapy ADT with a gonadotropin releasing hormone GnRH agonist or antagonist for at least 6 months before randomization total serum testosterone level of 50 ng/dL 1.72 nmol/L hormone refractory androgen independent prostate cancer demonstrated during continuous ADT/post-orchiectomy defined as - 3 consecutive PSA values with PSA1 PSA2 PSA3 - each PSA value must be separated by at least 2 weeks - PSA2 and PSA3 .1.0 ng/mL high risk for development of bone metastasis - PSA value .8.0 ng/mL, obtained no more than 3 months before randomization OR - PSA doubling time .10.0 months calculated per Section 7.8 adequate organ function, as defined by the following criteria - Serum aspartate aminotransferase AST .2.5 x upper limit of normal ULN - Serum alanine aminotransferase ALT .2.5 x ULN - Serum total bilirubin .1.5 x ULN - Serum calcium or albumin-adjusted serum calcium .2.0 mmol/L 8.0 mg/dL and .2.9 mmol/L 11.5 mg/dL before any study-specific procedure, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
Exclusion Criteria prior or current evidence of radiographically detectable bone metastasis known prior or current evidence of any metastatic involvement of distant organs lymph node metastases in any region is acceptable prior or current IV bisphosphonate administration prior or current use of oral bisphosphonates as follows - greater than or equal to 3 years Page 6 of 98 continuously - greater than 3 months but less than 3 years eligible if subject has a 1 year washout before randomization prior administration of denosumab prior history or current evidence of osteomyelitis or osteonecrosis of the jaw evidence of any of the following conditions per subject self report or medical chart review - any prior malignancy other than treated basal cell skin cancer , within 5 years before randomization - major surgery or significant traumatic injury occurring within 4 weeks before randomization - active infection with Hepatitis B virus or Hepatitis C virus - known infection with human immunodeficiency virus HIV any major medical or psychiatric disorder that in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results thirty days or less since receiving an investigational product or device in another clinical trial. known sensitivity to any of the products to be administered during the study eg, mammalian derived products, calcium or vitamin D |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint bone metastasis-free survival determined by the time to first occurrence of bone metastasis either symptomatic or asymptomatic or death from any cause. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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.8.3 |
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 | 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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |