E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low-volume Metastatic Hormone-sensitive Prostate Cancer (mHSPC) |
Cáncer de próstata metastásico hormonosensible (CPmHS) de baja carga tumoral |
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E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer |
Cáncer de Próstata |
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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 | 18.1 |
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 if JNJ-56021927 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) |
Determinar si JNJ-56021927 junto con el agonista de la hormona liberadora de gonadotropina (GnRH) en pacientes con cáncer de próstata de alto riesgo localizado o localmente avanzado que están recibiendo radioterapia (RT) primaria produce una mejora de la supervivencia sin metástasis (SSM) evaluada mediante una revisión central independiente y enmascarada (RCIE). |
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E.2.2 | Secondary objectives of the trial |
- To characterize the safety profile of JNJ-56021927 plus GnRH agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary RT - To determine if JNJ-56021927 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) |
Determinar si JNJ-56021927 junto con un agonista de la GnRH en pacientes con cáncer de próstata de alto riesgo localizado o localmente avanzado que están recibiendo RT primaria produce una mejora de: - Tiempo hasta la recurrencia local-regional - Tiempo hasta el cáncer de próstata resistente a la castración (CPRC) - Tiempo hasta la metástasis a distancia - La supervivencia global (SG) |
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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, 2) Gleason score >=7, PSA >=20 nanogram per mililiters (ng/mL), and >=cT2c - Charlson comorbidity index (CCI) <=3 - An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1 - Adequate liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), <2 * upper limit of normal (ULN) and total bilirubin <1.5 * ULN - 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 |
Varones >= 18 años de edad - Todos los pacientes deben firmar un documento de consentimiento informado (DCI) que indique que entienden el objetivo del estudio y los procedimientos que exige y que están dispuestos a participar en él y a cumplir las prohibiciones y restricciones que se especifican en este protocolo (Sección 4.3). - Indicado y previsto que reciba RT primaria para el cáncer de próstata. - Diagnóstico confirmado, histológica o citológicamente, de adenocarcinoma de próstata intacta y una de las siguientes observaciones en el momento del diagnóstico: 1) Puntuación de Gleason >=8 y >=cT2c 2) Puntuación de Gleason >=7, PSA >=20 ng/ml, y >=cT2c - Índice de comorbididad de Charlson (CCI) <=3 (Anexo 1) - Estado funcional (EF) del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 (Anexo 2). 7. Función hepática suficiente determinada por los siguientes valores del laboratorio central: Aspartato-aminotransferasa (AST)/alanina-aminotransferasa (ALT) < 2 x límite superior de la normalidad (LSN) y Bilirrubina total <1,5 x límite superior de la normalidad (LSN) [NOTA: En los pacientes con síndrome de Gilbert, si la bilirrubina total es >1,5 x LSN, hay que medir la bilirrubina directa e indirecta y, si la bilirrubina directa es 1,5 x LSN, el paciente es apto para el estudio] - Con el fin de evitar el riesgo de exposición al fármaco a través del eyaculado (incluso los varones con vasectomía), los pacientes deben usar un preservativo durante las relaciones sexuales mientras reciban el fármaco del estudio y durante 3 meses después de la última dosis de dicho medicamento. No se permite donar semen durante la fase de tratamiento y en los 3 meses siguientes a la última dosis del medicamento del estudio. - Deben ser capaces de tragar enteros los comprimidos de fármaco del estudio. |
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E.4 | Principal exclusion criteria |
- Presence of distant metastasis, including pelvic nodal disease below the iliac bifurcation >2 cm in the short axis - 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 procedural (eg, prostatectomy, cryotherapy) treatment for prostate cancer - History of seizure or 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 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 is 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 JNJ-56021927, 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 |
- Presencia de metástasis a distancia, incluida enfermedad nodal pélvica por debajo de la bifurcación ilíaca > 2 cm en el eje corto - Tratamiento previo con un análogo de la GnRH o antiandrogénico o ambos > 3 meses antes de la aleatorización Orquiectomía bilateral - Antecedentes de irradiación pélvica - Tratamiento previo sistémico (por ejemplo, quimioterapia) o mediante algún procedimiento (por ejemplo, prostatectomía, crioterapia) para el cáncer de próstata - Tratamiento previo con enzalutamida, acetato de abiraterona, orteronel, galeterona, ketoconazol, aminoglutetimida, estrógenos, acetato de megestrol y agentesprogestágenos para el cáncer de próstata - Tratamiento previo con agentes radiofarmacéuticos (por ejemplo, estroncio-89) o inmunoterapia (por ejemplo, sipuleucel-T) para el cáncer de próstata - Tratamiento previo con glucocorticoides sistémicos 4 semanas antes de la aleatorización o probabilidad de que vaya a necesitar uso a largo plazo de corticosteroides durante el estudio - Uso de inhibidores de la 5-reductasa (por ejemplo, dutasterida, finasterida) 4 semanas antes de la aleatorización - Uso de cualquier fármaco en investigación 4 semanas antes de la aleatorización - Uso crónico presente de analgésicos opioides durante 3 semanas para fármacos orales o 7 días para formulaciones no orales - Cirugía mayor 4 semanas previas a la aleatorización - Antecedentes de crisis convulsiva o de trastorno que predisponga a estas crisis (entre ellos, accidente cerebrovascular previo, accidente isquémico transitorio o pérdida del conocimiento 1 año antes de la aleatorización; malformación arteriovenosa cerebral; o masas intracraneales, como schwannoma o meningioma, que produzcan edema o efecto de masa). - Tratamiento actual o previo con antiepilépticos para las crisis convulsivas - Afecciones digestivas que afecten a la absorción - Posibles contraindicaciones o contraindicaciones confirmadas o hipersensibilidad a JNJ-56021927, bicalutamida o a agonistas de la GnRH oa cualquiera de los componentes de las formulaciones - Todo trastorno que, en opinión del investigador, haría que la participación en el estudio no sería lo mejor para el paciente |
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E.5 End points |
E.5.1 | Primary end point(s) |
Metastasis-free survival |
Supervivencia libre de metástasis |
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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) |
- Tiempo hasta la recurrencia local-regional - Tiempo hasta el cáncer de próstata resistente a la castración (CPRC) - Tiempo hasta la metástasis a distancia - Supervivencia global (SG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 72 Months - 72 Months - 72 Months - 72 Months |
- 72 Meses - 72 Meses - 72 Meses - 72 Meses |
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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 | 12 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Czech Republic |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
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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LVLS |
Última visita del último paciente |
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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 | |
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 | 7 |