E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients With Nonmetastatic 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 enzalutamide compared with placebo as assessed by metastasis free survival (MFS). |
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E.2.2 | Secondary objectives of the trial |
* To evaluate the benefit of enzalutamide compared with placebo as measured by the following:
-Time to (PSA) progression
-Time to first use of new antineoplastic therapy
-Overall survival
-Time to pain progression
-Time to first use of cytotoxic chemotherapy
-Chemotherapy-free disease-specific survival
-Chemotherapy-free survival
-PSA response rates
-Quality of life as assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) health questionnaire, and Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) module
*To evaluate safety
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age 18 years or older and willing and able to provide informed consent;
2.Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features;
3.Ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);
4.Testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening;
5.For patients receiving bisphosphonates or denosumab, dose must be stable for at least 4 weeks before randomization;
6.Progressive disease on androgen deprivation therapy at enrollment defined as a minimum of 3 rising PSA values (PSA1 < PSA2 < PSA3) assessed by a local laboratory (local PSA) with an interval of ≥ 1 week between each determination.
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E.4 | Principal exclusion criteria |
1.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);
2.Treatment with hormonal therapy (eg, androgen receptor inhibitors, estrogens, 5 alpha reductase inhibitors) or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) within 4 weeks of randomization;
3.Use of an investigational agent within 4 weeks of randomization;
4.Known or suspected brain metastasis or active leptomeningeal disease;
5.History of another invasive cancer within 3 years of randomization, with the exception of fully treated cancers with a remote probability of recurrence in the opinion of both the medical monitor and investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Metastasis free survival (MFS), assessed by blinded independent central radiology review. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MFS is defined as the time from randomization to radiographic progression or death on study (death within 112 days of treatment discontinuation without evidence of radiographic progression), whichever occurs first. |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoints:
-Time to PSA progression
-Time to first use of new antineoplastic therapy
-Overall survival
Additional Secondary Endpoints are as follows:
-Time to pain progression
-Time to first use of cytotoxic chemotherapy
-Chemotherapy-free disease specific survival
-Chemotherapy-free survival
-PSA response rates
-Quality of life as assessed by FACT-P questionnaire, EQ-5D-5L, Health Questionnaire, and QLQ-PR25 Module
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The single MFS analysis will be performed approximately after 440 MFS events occur. All secondary endpoints will be evaluated for efficacy at this time. |
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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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
China |
Denmark |
Finland |
France |
Germany |
Greece |
Hong Kong |
Italy |
Korea, Republic of |
Malaysia |
Netherlands |
New Zealand |
Poland |
Russian Federation |
Serbia |
Singapore |
Slovakia |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
Ukraine |
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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Study drug administration should continue until radiographic progression as specified in the protocol. |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |