E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Prostate Cancer |
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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 | 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effectiveness of niraparib plus AA-P compared to AA-P plus placebo. |
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E.2.2 | Secondary objectives of the trial |
* To assess the clinical benefit of niraparib plus AA-P compared to AA-P plus placebo * To characterize the safety profile of niraparib when given with AA-P compared to AA-P with placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. DRD status (identified by the sponsor’s required assays) 2. Metastatic disease documented by radiographic imaging 4. Able to continue GnRHa during the study if not surgically castrate 5. ECOG PS Grade of 0 or 1 6 Score of ≤3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours). 7. Adequate clinical laboratory values at Screening |
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E.4 | Principal exclusion criteria |
1. Prior treatment with a PARP inhibitor 2. No prior systemic therapy for mCRPC except for GnRHa and limited AA-P 4. Symptomatic brain metastases 5. History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) 6. Other prior malignancy ≤2 years prior to randomization, or malignancy that currently requires active systemic therapy 7. Severe or unstable angina, myocardial infarction or ischemia requiring coronary artery bypass graft or stent within the previous 6 months, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g. adequate cardiac function), or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) Class II to IV heart disease 8. Presence of uncontrolled hypertension 9. Current evidence of any of the following: a. Any medical condition that would make prednisone use contraindicated b. Any chronic medical condition requiring a higher equivalent dose of corticosteroid than 10 mg prednisone (or equivalent) per day 11. History of adrenal dysfunction 13. Subjects who are receiving opioid analgesics at the time of screening 14. Active human immunodeficiency virus (HIV) infection |
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E.5 End points |
E.5.1 | Primary end point(s) |
Radiographic progression-free survival (rPFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
While on study treatment, radiographic imaging will be performed every 8 weeks for the first 6 months and every 12 weeks thereafter |
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E.5.2 | Secondary end point(s) |
* OS * Time to chronic opioid use * Time to pain progression * Time to initiation of cytotoxic chemotherapy
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments of the secondary endpoints are variable but carried out on a regular basis from C1D1 through the follow up as described in the endpoint requirements |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker evaluations, PRO |
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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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 156 |
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 |
China |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Poland |
Portugal |
Russian Federation |
South Africa |
Spain |
Sweden |
Taiwan |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 24 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 24 |