E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 21.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036920 |
E.1.2 | Term | Prostate cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036911 |
E.1.2 | Term | Prostate cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036912 |
E.1.2 | Term | Prostate cancer stage 0 |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036917 |
E.1.2 | Term | Prostate cancer stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036919 |
E.1.2 | Term | Prostate cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036918 |
E.1.2 | Term | Prostate cancer stage II |
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 |
Analyse the effects of short term (3 months) enzalutamide on distinct AR-chromatin binding patterns in correlation with tissue proliferation in normal prostate tissue and prostate cancer. |
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E.2.2 | Secondary objectives of the trial |
= To assess the effects of 3 months enzalutamide pretreatment on down-staging
= Study the correlation between AR-chromatin binding alterations and Ki-67 expression.
= Compare the AR-chromatin binding with expression alterations of known AR-dependent genes such as PSA, human kallikrein and PSMA.
= Compare AR-chromatin binding patterns with gleason grading.
= Confirm findings of associated genes on TMA derived from prostatectomy specimens.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men over 18 years of age.
2. clinically non-metastasized prostate cancer, tumor that can be imaged (TRUS or MRI) in order to allow for accurate preoperative biopsies.
3. Gleason score 7-10
4. written informed consent
5. WHO performance 0-1
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E.4 | Principal exclusion criteria |
1. A history of seizures
2. Clinically nodal metastases
3. Prostatitis or urinary tract infection
Androgen ablative therapy within 6 weeks of inclusion (including 5 alpha-reductase inhibitors)
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E.5 End points |
E.5.1 | Primary end point(s) |
To identify AR chromatin binding patterns and downstream responsive genes that hallmark distinct sensitivity to enzalutamide treatment in prostate cancer, as well as the dynamics thereof before and after treatment. To analyze the effects of the novel antiandrogen enzalutamide on AR-responsive gene expression, tumor samples will be assessed before (biopsy) and after (resection) 3 months of neoadjuvant androgen ablation, and PSA and KI-67 (cell proliferation marker) levels will be determined by immunohistochemistry. We selected 3 months of treatment based on the fact that earlier data showed AR/DNA binding alterations after several weeks of treatment. Moreover, 3 months is a practical period of time for preparation for the surgical procedure, does not expose men to the side-effects of antiandrogen ablation longer then necessary, and does not seem to compromise outcome in those men that may not respond to antiandrogen ablation. Patients will be stratified on alterations in PSA and/or KI-67 to identify alterations in AR genomic profile and downstream regulated genes that correlate with response to androgen ablation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From start of treatment until 3 months after end of treatment |
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E.5.2 | Secondary end point(s) |
2. The effects of 3 months enzalutamide on tumor staging as assessed by clinical staging and pathological staging. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From start of treatment until 3 months after end of treatment |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |