E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy-Naïve Patients with Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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 |
Co-Primary Objectives: • To determine the benefit of MDV3100 as compared to placebo as assessed by overall survival; • To determine the benefit of MDV3100 as compared to placebo as assessed by radiographic progression-free survival (rPFS).
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives: • To determine the benefit of MDV3100 as compared to placebo as assessed by time to first skeletal-related event; • To determine the benefit of MDV3100 as compared to placebo as assessed by time to initiation of cytotoxic chemotherapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment. Eligible patients must meet all inclusion criteria. 1. Received randomized double-blind treatment in PREVAIL; 2. Open-label day 1 visit is within 6 months after this amendment is approved and becomes effective at the study site; 3. Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy; 4. Is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study; |
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E.4 | Principal exclusion criteria |
The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must NOT meet any of the following criteria: 1. Is taking commercially available enzalutamide (Xtandi); 2. Has any clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic, psychological, pulmonary, or renal disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator or medical monitor; 3. Has current or previously treated brain metastasis or active leptomeningeal disease; 4. Has a history of seizure or a condition that may increase the risk of seizure; 5. Has total bilirubin ≥ 1.5-times the upper limit of normal (ULN) (except patients with a diagnosis of Gilbert's disease); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5-times ULN at screening. For patients with documented liver metastases, ALT and AST exclusion is > 5-times ULN; 6. Has creatinine > 2 mg/dL (177 μmol/L) at screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival and Radiographic Progression Free Survival
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall Survival: Time from randomization to death due to any cause will be assessed.
Radiographic Progression-Free Survival: Time from randomization to the first objective evidence of radiologic progression or death due to any cause (whichever occurs first) will be assessed. |
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E.5.2 | Secondary end point(s) |
Time to First Skeletal-Related Event
Time to Initiation of Cytotoxic Chemotherapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time to First Skeletal-Related Event: Time from randomization to first skeletal-related event will be assessed.
Time to Initiation of Cytotoxic Chemotherapy: Time from randomization to initiation of cytotoxic chemotherapy will be assessed. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | No |
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 |
Austria |
Belgium |
Canada |
Denmark |
Finland |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Netherlands |
Poland |
Russian Federation |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |