E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration Resistant Prostate Cancer (mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Prostate Cancer |
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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 | 19.1 |
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 | 19.1 |
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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory 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 |
Primary Objectives:
To explore whether the decrease in a panel of early easily assessable biomarkers (PSA-mRNA, PCA3-mRNA and TMPRSS2:ERG gene fusion-mRNA, (currently under development) ARv7 mRNA, ARwt mRNA, miR-21, miR-141, miR-200a, miRrumc95, miRrumc87 and miRrumc4417) can discriminate between patients who will develop 1. Objective response 2. Stable disease and 3 who are de novo resistant after 3 and 6 months of therapy.
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
- To explore the relation between enzalutamide & N-desmethylenzalutamide plasma exposure and the decrease in the se-lected biomarkers (the panel of mRNAs and microRNAs)
- To explore the relation between selected biomarker response under enzalutamide therapy and radiographic progression free survival
- To explore the relation between enzalutamide & N-desmethylenzalutamide exposure and radiographic progression free survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
- Male patients with metastatic castration resistant prostate cancer* who are chemotherapy naive OR have been treated upfront with 6 cycles of docetaxel: conform the Chaarted or Stampede trials
- Age at least 18 years
- Patients from who it is possible to collect blood samples
- Patient who are able and willing to give written informed consent prior to screening and enrollment
- Life expectancy of > 6 months
- Measurable disease
*definition of CRPC according to EAU guidelines 2014
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E.4 | Principal exclusion criteria |
The study objective is to explore the effect of enzalutamide on biomarker exposure in a group of patients treated with enzalutamide in agreement with the drug label. Therefore no strict exclusion criteria will be used in this study.Additionally, patients are not allowed to be treated with other anti-cancer therapies, concomitant alternative therapies and herbal preparations that potentially affect enzalutamide exposure and strong CYP2C8 inhibitors and inducers
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E.5 End points |
E.5.1 | Primary end point(s) |
To describe the relation between (early)biomarker response (%) and therapeutical response (OR, SD, de novo resistent) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Response Assessment: Day 84(±4d) ; Day 168(±4d)
Biomarkers : Day 28(±2d) ; Day 84(±4d) ; Day 168(±4d)
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E.5.2 | Secondary end point(s) |
- To explore the relation between Enzalutamide&N-desmethylenzalutamide exposure (AUC) and decrease in biomarkers(%) from baseline
- To describe the relation between biomarker response en rPFS
- To describe the relation between (early) drug exposure and therapeutical response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Response Assessment: Day 84(±4d) ; Day 168(±4d)
Biomarkers : Day 28(±2d) ; Day 84(±4d) ; Day 168(±4d)
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | 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 | 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
| 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 | 8 |
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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |