E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk localized or locally advanced prostate cancer |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 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) |
|
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 if treatment with ADT plus apalutamide (with or without AAP) before and after radical prostatectomy in subjects with high-risk localized or locally advanced prostate cancer results in an improvement in pCR rate and MFS, as compared to ADT plus placebo |
|
E.2.2 | Secondary objectives of the trial |
-To determine if treatment with ADT plus apalutamide (with or without AAP) before and after radical prostatectomy in subjects with high risk localized or locally advanced prostate cancer results in improvement of other efficacy endpoints, as compared to ADT plus placebo
- To characterize the safety profile of treatment with ADT plus apalutamide (with or without AAP) before and after radical prostatectomy in subjects with high risk localized or locally advanced prostate cancer
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must be ≥18 years of age 2. Signed an informed consent form (ICF) indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 4.3) 3. Histologically confirmed adenocarcinoma of the prostate 4. High risk defined by ≥1 of the following 4 criteria: • Any combination of Gleason score 4+3 and 4+4 from ≥6 systematic cores • Any combination of Gleason score 4+3 and 4+4 from ≥3 systematic cores and PSA ≥20 ng/mL • Gleason score ≥9 in at least one systematic or targeted core • At least 2 systematic or targeted cores with continuous Gleason score ≥8, each with ≥ 80% involvement 5. Candidate for radical prostatectomy as per the investigator 6. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 7. Adequate organ function determined by the following central laboratory values: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin less than the upper limit of normal (ULN; note that in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible) b. Serum creatinine <1.5 mg/dL c. Platelets ≥75,000/uL, without transfusion and/or growth factors within 1 month prior to randomization d. Hemoglobin ≥12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization 8. Able to receive ADT for up to 1 year, per the investigator’s assessment 9. Be able to swallow whole study drug tablets and capsules 10. Contraceptive (birth control) use by men (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies. |
|
E.4 | Principal exclusion criteria |
1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0 2. Prior treatment with anti-androgen 3. Prior treatment for prostate cancer 4. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate 5. Bilateral orchiectomy 6. History of any pelvic radiation 7. Use of any investigational agent ≤4 weeks prior to randomization 8. Major surgery ≤4 weeks prior to randomization 9. Any of the following within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary 10. Human immunodeficiency virus-positive subjects with 1 or more of the following: a. Not receiving highly active antiretroviral therapy b. Had a change in antiretroviral therapy within 6 months of the start of screening c. Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment) d. CD4 count <350 at screening e. AIDS-defining opportunistic infection within 6 months of start of screening 11. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction 12. History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect) 13. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization 14. Gastrointestinal conditions affecting absorption 15. Known or suspected contraindications or hypersensitivity to apalutamide, abiraterone acetate, GnRH agonists or any of the components of the formulations 16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. pCR rate (assessed by blinded independent pathological review) 2. MFS (evaluated by blinded independent central review [BICR])
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. at radical prostatectomy 2. until documented distant metastasis, death, lost to follow-up, withdrawal of consent, or termination of the study by the sponsor, whichever occurs first |
|
E.5.2 | Secondary end point(s) |
1. PSA-free survival 2. Progression-free survival (PFS) 3. Adverse events (AEs), clinical laboratory tests, and treatment compliance
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with lymph node dissection (RPLND) or death, whichever occurs first 2. time from randomization to first documentation of BICR-confirmed radiographic progressive disease or death due to any cause (whichever occurs first) + 1 day 3. from signing of consent until 30 days after last dose of study drug. Clinical Labs & compliance per T&E on treatment |
|
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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers and tolerability |
|
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 | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 |
Canada |
China |
Czech Republic |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 9 |