E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Hormone-Naive Prostate Cancer (mHNPC) |
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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 | 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether abiraterone acetate in combination with low-dose prednisone and androgen deprivation therapy (ADT) is superior to ADT alone in improving rPFS and OS in subjects with mHNPC with high-risk prognostic factors. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the clinically relevant improvements as well as the safety of abiraterone acetate plus low-dose prednisone and ADT compared to ADT alone. •To identify microRNA (miRNA) and mRNA profiles predictive of abiraterone acetate response or resistance in this patient population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology 2. Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography or magnetic resonance imaging scan 3. At least two of the following high-risk prognostic factors: Gleason score of >=8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI scan based on RECIST 1.1. 4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2 5. Adequate hematologic, hepatic, and renal function 6. Agrees to protocol-defined use of effective contraception
Treatment Criteria for Crossover to the Open-label Extension Phase: 1. Subject is receiving study drug and is willing and able to provide written informed consent to crossover to open-label abiraterone acetate plus prednisone therapy 2. Adequate hepatic and safety laboratory assessments below within 4 weeks of OLE Phase Cycle 1 Day 1: • total bilirubin ≤1.5X upper limit of normal (ULN) (except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN) • alanine (ALT) and aspartate (AST) aminotransferase ≤2.5X ULN • serum potassium ≥3.5 mM. If a subject has a serum potassium level <3.5 mM, he could be given adequate potassium supplement and retested. Once the serum potassium level is ≥3.5 mM after adequate treatment with a potassium supplement, the subject would be eligible for enrollment in the OLE Phase. |
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E.4 | Principal exclusion criteria |
1. Active infection or other medical condition that would make prednisone use contraindicated 2. Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day 3. Pathological finding consistent with small cell carcinoma of the prostate 4. Known brain metastasis 5. Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer; the following exceptions are permitted: up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or orchiectomy with or without concurrent anti-androgens prior to Cycle 1 Day 1; participants may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1, all adverse events associated with these procedures must be resolved at least to Grade 1 by Cycle 1 Day 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Overall survival 2)Radiographic progression-free survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up toMonth 60 (5 years)
2) Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up toMonth 60 (5 years) |
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E.5.2 | Secondary end point(s) |
1) Time to subsequent therapy for prostate cancer 2) Time to initiation of chemotherapy 3) Time to prostate specific antigen progression 4) Time to next skeletal-related event 5) Time to pain progression |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 & 2) From randomization to time to the occurrence of each event (up to Month 60) 3) Cycles 1-13 Day 1, Day 1 every other cycle starting Cycle 14 to end-of-treatment up to disease progression 4) From randomization to time to the occurrence of one of the following: clinical fracture, spinal cord compression, palliative radiation to bone, surgery to bone, up to month 60. 5) Up to month 60. |
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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 | Yes |
E.8.2.3.1 | Comparator description |
LHRH agonists or orchiectomy |
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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 | 123 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Turkey |
Ukraine |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |