E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients With Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer. |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
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 determine the efficacy of combination treatment with continued enzalutamide plus abiraterone acetate (abiraterone) and prednisone (or prednisolone) compared with placebo plus abiraterone and prednisone as measured by progression free survival (PFS) after prostate-specific antigen (PSA) progression on treatment with enzalutamide in patients with chemotherapy-naive metastatic castration-resistant prostate cancer
(CRPC). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of combination treatment with continued enzalutamide plus abiraterone and prednisone compared with placebo plus abiraterone and prednisone after PSA progression on treatment with enzalutamide in patients with chemotherapy naïve metastatic CRPC on the following: Time to PSA progression, PSA response, objective response rate, rate of pain progression, time to first use of subsequent antineoplastic therapy for prostate cancer, quality of life and safety.
Supplement 1 Study Objectives:
To offer treatment access under Supplement 1 to all active and eligible patients for as long as there is clinical benefit as assessed by the treating physician based on clinical, laboratory and imaging data.
To ensure continued safety monitoring to patients enrolled under Supplement 1, which will be conducted by local standard of care. |
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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 |
Optional blood-based biomarker substudy: To analyze candidate
biomarkers in circulation for association with response or progression
and for identifying mechanisms of resistance |
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E.3 | Principal inclusion criteria |
Age 18 years or older and willing and able to provide informed consent;
Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, or signet cell or small cell features;
Presence of metastatic disease as assessed by CT/MRI and/or whole body radionuclide bone scan;
Throughout study, ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);
Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening;
Progressive disease on androgen deprivation therapy at screening defined as a minimum of 3 sequential rising PSA values (PSA1 < PSA2 < PSA3) assessed by the local laboratory (local PSA) with an interval of ≥ 1 week between each determination;
The most recent local PSA and the screening PSA assessed by the central laboratory should be ≥ 2 µg/L (≥ 2 ng/mL). In the event of prior androgen receptor inhibitor use, the most recent local PSA and the screening PSA assessed by the central laboratory (central PSA) must be obtained at least 4 weeks after the last dose of the androgen receptor inhibitor.
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E.4 | Principal exclusion criteria |
Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo);
Medical contraindication to prednisone use; Treatment with hormonal therapy (eg, androgen receptor inhibitors, 5 alpha reductase inhibitors) or biologic therapy for prostate cancer (other than denosumab, GnRH agonist/antagonist therapy, or corticosteroid therapy) within 4 weeks of screening;
Use of an investigational agent within 4 weeks of the screening visit;
Current or previously treated brain metastasis or active leptomeningeal disease.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS is defined as the time from randomization to the earliest objective evidence of radiographic progression, unequivocal clinical progression, or death on study (death within 112 days of treatment discontinuation without objective evidence of radiographic progression), whichever occurs first. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time to PSA progression is defined as the time from randomization to the date of the first PSA value demonstrating progression, which must be subsequently confirmed. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Period 1: enzalutamide open-label treatment |
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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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
United States |
Belgium |
Denmark |
Finland |
France |
Italy |
Slovakia |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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Study drugs will continue until disease progression (as defined by radiographic imaging or unequivocal clinical progression), intolerable toxicity, patient withdrawal, or death on study, whichever occurs first. |
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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 | 11 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 11 |