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 | 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 demonstrate a relation of abiraterone exposure (area under the curve) with treatment response (following RECIST criteria for complete remission, partial remission and stable disease, primarily based on radiographic response and secondary on biochemistry (≥25% decrease in PSA). |
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E.2.2 | Secondary objectives of the trial |
-To explore the relation between novel early and easily assessable biomarkers (PSA-mRNA, PCA3-mRNA, TMPRSS2:ERP gene fusion-mRNA, (currently under development)ARv7 mRNA and ARwt mRNA) and treatment response after 3 months and 6 months of therapy
-To explore whether the degree of reductions of these novel biomarkers are related to abiraterone exposure (AUC) after 3 and 6 months of therapy
-To explore the relation between traditional PD biomarkers (serum PSA, DHEA, LDH, AP) and treatment response after 3 and 6 months of therapy
-To explore whether the degree of reductions in PSA, DHEA, LDH, AP are related to abiraterone exposure (AUC) after 3 and 6 months of therapy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- patients with metastatic castration resistant prostate cancer* who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated – OR – who have been treated upfront with 6 cycles of docetaxel: conform the Chaarted or Stampede trials- Age ≥18 years
- Feasible to collect blood samples from
- Life expectancy of > 6 months
- Measurable disease
- Able and willing to give written informed consent prior to screening and enrollment
*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 abiraterone exposure on treatment and biomarker response in group of patients treated with abiraterone acetate in agreement with the drug label. Therefore the exclusion criteria as listed in the package insert will be used in this study. Additionally, patients are not allowed to be treated with other anticancer therapies, potent CYP3A4 inhibitors or inducers and herbal medicine that could interfere with abiraterone exposure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate a relation of abiraterone exposure (area under the curve) with treatment response |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Respons Assessment: Day 84(±4d) ; Day 168(±4d)
Pharmacokinetics: 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 novel early and easily assessable biomarkers (PSA-mRNA, PCA3-mRNA, TMPRSS2:ERP gene fusion-mRNA, (currently under development)ARv7 mRNA and ARwt mRNA) and treatment response after 3 months and 6 months of therapy
-To explore whether the degree of reductions of these novel biomarkers are related to abiraterone exposure (AUC) after 3 and 6 months of therapy
-To explore the relation between traditional PD biomarkers (serum PSA, DHEA, LDH, AP) and treatment response after 3 and 6 months of therapy
-To explore whether the degree of reductions in PSA, DHEA, LDH, AP are related to abiraterone exposure (AUC) after 3 and 6 months of therapy
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacodynamics(biomarkers assessment): Day 28(±2d) ; Day 84(±4d) ; Day 168(±4d)
Pharmacokinetics: Day 28(±2d) ; Day 84(±4d) ; Day 168(±4d)
Treatment response: 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) | 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
| 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 | 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 | 3 |
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 | 3 |