E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High- or very-high risk, localized or locally advanced prostate cancer |
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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 | 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) |
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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 if apalutamide plus gonadotropin releasing hormone (GnRH) agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT) results in an improvement of metastasis-free survival (MFS) evaluated by blinded independent central review (BICR) |
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E.2.2 | Secondary objectives of the trial |
- To characterize the safety profile of apalutamide plus GnRH agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary RT
- To determine if apalutamide plus GnRH agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary RT results in an improvement of:
* Time to local-regional recurrence
* Time to castration-resistant prostate cancer (CRPC)
* Time to distant metastasis
* Overall survival (OS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years
- Indicated and planned to receive primary radiation therapy for prostate cancer
- Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis:
1) Gleason score >=8 and >=cT2c stage per AJCC 8th Edition,
2) Gleason score 7, PSA >=20 nanogram per mililiters (ng/mL), and >=cT2c stage per AJCC 8th Edition
- Charlson comorbidity index (CCI) <=3
- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
- Adequate organ function determined by the following central laboratory values:
1) aspartate aminotransferase (AST), alanine aminotransferase (ALT) within normal limits (WNL)
2) total bilirubin WNL
3) Serum creatinine <1.5 mg/dL (<133 μmol/L)
4) Platelets ≥140,000/μL, independent of transfusion and/or growth factors within 3 months prior to randomization
5) Hemoglobin ≥ 12.0 g/dL (7.4 mmol), independent of transfusion and/or growth factors within 3 months prior to randomization
- Participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial
- Signed, written, informed consent
- Be able to swallow whole study drug tablets |
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E.4 | Principal exclusion criteria |
- Presence of distant metastasis (clinical stage M1). Isolated pelvic 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.
- Prior treatment with GnRH analogue or antiandrogen or both for >3 months prior to randomization
- Bilateral orchiectomy
- History of pelvic radiation
- Prior systemic (eg, chemotherapy) or local (eg, radical prostatectomy, cryotherapy) treatment for prostate cancer
- 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)
- Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer
- Prior treatment with radiopharmaceutical agents (eg, strontium 89) or immunotherapy (eg, sipuleucel-T) for prostate cancer
- Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or subject expected to require long-term use of corticosteroids during the study
- Use of 5-alpha reductase inhibitors (eg, dutasteride, finasteride) <=4 weeks prior to randomization
- Use of any investigational agent <=4 weeks prior to randomization
- Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for non-oral formulations
- Major surgery <=4 weeks prior to randomization
- Current or prior treatment with antiepileptic medications for the treatment of seizures
- Gastrointestinal conditions affecting absorption
- Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or GnRH agonists or any of the components of the formulations
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to Local-regional Recurrence
- Time to Castration-resistant Prostate Cancer (CRPC)
- Time to Distant Metastasis
- Overall Survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 72 Months
- 72 Months
- 72 Months
- 72 Months |
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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 | 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 | 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) | 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) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 375 |
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 |
Brazil |
Canada |
China |
Israel |
Korea, Republic of |
Malaysia |
Mexico |
Taiwan |
United States |
France |
Poland |
Sweden |
Bulgaria |
Netherlands |
Romania |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Russian Federation |
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 | 9 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |