E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-Resistant Prostrate Cancer (mCRPC) |
Cancer de Prostata Metastasico resistente a la castracion (CPRCm) |
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E.1.1.1 | Medical condition in easily understood language |
mCRPC is prostate cancer that is resistant to medical (e.g., hormonal) or surgical treatments that lower testosterone, and has spread to other parts of the body |
CPRCm es el cancer de prostata que es resistente al tratamiento médico (ej: hormonal) o quirurgico que reducen la testosterona, y que ha invadido otras partes del cuerpo |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant 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 evaluate the efficacy of atezolizumab/enzalutamide compared with enzalutamide alone |
Evaluar la eficacia de atezolizumab/enzalutamida comparado con enzalutamida sola |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of atezolizumab/enzalutamide compared with enzalutamide alone -To evaluate the safety and tolerability of atezolizumab/enzalutamide compared with enzalutamide alone -To characterize the pharmacokinetics (PK)of atezolizumab when given in combination with enzalutamide -To characterize the PK of enzalutamide and its active metabolite N-desmethyl enzalutamide when enzalutamide is administered alone or in combination with atezolizumab -To evaluate the immune response to atezolizumab |
-Evaluar la eficacia de atezolizumab/enzalutamida comparado con enzalutamida sola -Evaluar la seguridad y la tolerancia de atezolizumab/enzalutamida comparado con enzalutamida sola -Definir la farmacocinética de atezolizumab cuando se administra en combinación con enzalutamida -Definir la farmacocinética de enzalutamida y su metabolito activo N-desmetil enzalutamida cuando se administra sola o en combinación con atezolizumab -Evaluar la respuesta inmune contra atezolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Eastern Cooperative Oncology Group performance status of 0 or 1 - Life expectancy >= 3 months - Histologically confirmed adenocarcinoma of the prostate - Progressive, castrate-resistant disease prior to screening by prostate-specific antigen (PSA) or imaging per prostate cancer working group 3 (PCWG3) criteria during or following the direct prior line of therapy in the setting of medical or surgical castration - One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen - One prior regimen/line of an androgen synthesis inhibitor for mCRPC - Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death ligand 1 (PD L1) status via central testing - Adequate hematologic and end organ function |
-Estado funcional ECOG 0 o 1 -Esperanza de vida >= 3 meses -Adenocarcinoma de próstata confirmado histológicamente -Progresión de la enfermedad antes de la selección en el estudio, determinada basándose en el nivel de PSA o los estudios por imágenes de acuerdo con los criterios PCWG3, durante o después del régimen de tratamiento previo más reciente en el entorno de la castración clínica o quirúrgica. -Pacientes que han recibido un régimen/línea de tratamiento previo que incluía un taxano para CPRCm o que se nieguen o no sean aptos para recibir dicho tratamiento -Pacientes que han recibido un régimen/línea de tratamiento previo con un inhibidor de la síntesis androgénica para CPRCm -Disponibilidad de una muestra de tumor representativa de un área no irradiada previamente que sea apropiada para la determinación del estado del ligando 1 de muerte celular programada (PD-L1) mediante un análisis realizado en el laboratorio central -Función hematológica y de órganos diana adecuada, |
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E.4 | Principal exclusion criteria |
Cancer-specific exclusions - Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment - Treatment with abiraterone within 2 weeks prior to study treatment - Structurally unstable bone lesions suggesting impending fracture - Known or suspected brain metastasis or active leptomeningeal disease General medical exclusions - Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study Exclusion criteria related to atezolizumab - Active or history of autoimmune disease or immune deficiency - Prior allogeneic stem cell or solid organ transplantation - History of pulmonary fibrosis/inflammation - Positive HIV test, active hepatitis B or C virus infection, or active tuberculosis - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated (CTLA) 4, anti programmed death 1 (PD 1), and anti PD L1 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment - Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Exclusion criteria related to enzalutamide - History of seizure or any condition that may predispose to seizure including history of unexplained loss of consciousness or transient ischemic attack within 12 months prior to study treatment - Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor |
Criterios de exclusión específicos del cáncer: -Administración de cualquier terapia antineoplásica aprobada, incluyendo quimioterapia, inmunoterapia, radiofármacos u hormonoterapia (exceptuando abiraterona), en las 4 semanas previas al inicio del tratamiento del estudio -Administración de abiraterona en las 2 semanas previas al inicio del tratamiento del estudio -Lesiones óseas estructuralmente inestables que indiquen una fractura inminente -Metástasis cerebrales confirmadas o sospechosas o enfermedad leptomeníngea activa Criterios de exclusión por condiciones médicas generales: -Procedimientos de cirugía mayor que no sean con fines diagnósticos en las 4 semanas previas al inicio del tratamiento del estudio o que previsiblemente sean necesarios en el transcurso del estudio Criterios de exclusión relacionados con atezolizumab: -Enfermedades autoinmunes o inmunodeficiencias -Trasplante alogénico de células madre o trasplante de órganos sólidos -Antecedentes de fibrosis pulmonar/ inflamación -Resultado positivo en la prueba del VIH, Infección activa por virus de hepatitis B (VHB) o por virus de hepatitis C (VHC),Tuberculosis activa -Tratamiento previo con agonistas de CD137 o inhibidores de puntos de control inmunitarios, incluyendo anticuerpos terapéuticos anti-CTLA4, antiPD-1 y antiPD-L1 -Tratamiento sistémico con agentes inmunoestimuladores en las 4 semanas previas al inicio del tratamiento del estudio o durante cinco semividas del fármaco en ese período, dependiendo de lo que sea más corto -Tratamiento sistémico con inmunosupresores en las 2 semanas previas al inicio del tratamiento del estudio Criterios de exclusión relacionados con enzalutamida: -Antecedentes de convulsiones o cualquier condición que pueda predisponer a convulsiones, incluyendo antecedentes de pérdida de conciencia injustificada o ataque isquémico transitorio en los 12 meses previos al inicio del tratamiento del estudio -Tratamiento previo con enzalutamida u otros inhibidores hormonales del receptor androgénico |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Overall survival (OS) |
1.supervivencia global (SG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 42 months |
1 Hasta aproximadamente 42 meses |
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E.5.2 | Secondary end point(s) |
1.Time to cancer-related pain progression 2.Time to first symptomatic skeletal event 3.Radiographic progression-free survival (rPFS), as assessed by the investigator and adapted from the PCWG3 criteria 4.Immune-modified rPFS, as assessed by the investigator 5.PSA response rate 6.Time to PSA progression 7.Objective response rate determined by the investigator through use of PCWG3 criteria and immune modified response evaluation criteria in solid tumors criteria 8.Incidence, nature, frequency, and severity of adverse events, with severity determined through use of the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 9. Serum concentration of atezolizumab at specified timepoints 10. Plasma concentration of enzalutamide and N-desmethyl enzalutamide at specified timepoints in the safety run in phase and in a PK cohort in the randomized phase 11. Incidence of anti-therapeutic antibodies (ATAs) against atezolizumab |
1.Tiempo hasta la progresión del dolor relacionado con el cáncer 2.Tiempo al primer evento óseo sintomático 3.Supervivencia libre de progresión radiológica (SLPr), evaluada por el investigador y adaptada de los criterios PCWG3 4.SLPr de acuerdo con los criterios RECIST modificados basados en la respuesta inmune, evaluada por el investigador 5.Índice de respuesta basado en el PSA 6.Tiempo hasta la progresión del PSA 7.Índice de respuesta objetiva evaluado por el investigador de acuerdo con los criterios PCWG3 y los criterios RECIST modificados basados en la respuesta inmune 8.Incidencia, características, frecuencia y severidad (evaluada de acuerdo con los criterios NCI CTCAE v4.0) de los acontecimientos adversos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-8. Up to approximately 42 months 9. Cycle (C) 1 Day (D) 1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1; at atezolizumab discontinuation visit; and 120 days after last dose of atezolizumab 10. C1D1, C3D1, and C8D1 11. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1; at atezolizumab discontinuation visit; and 120 days after last dose of atezolizumab |
1-8 Hasta aproximadamente 42 meses 9. Ciclo(C)1 Dia (D)1,C2D1, C3D1, C4D1, C8D1, C12D1, C16D1; en visita de discontinuacion de Atezolizumab; y 120 dias tras ultima dosis de atezolizumab 10. C1D1, C3D1, y C8D1 11. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1;en visita de discontinuacion de Atezolizumab; y 120 dias tras ultima dosis de atezolizumab |
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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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
European Union |
France |
Germany |
Greece |
Hungary |
Italy |
Japan |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
Switzerland |
Taiwan |
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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The end of this study is defined as the earliest date of the following: • Receipt of last data point from the last patient • Sponsor decision to end the study |
El estudio terminará en la fecha en la que ocurra la primera de las circunstancias siguientes: Cuando se reciban los últimos datos del último paciente Cuando el promotor decida terminar el estudio |
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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 | |
E.8.9.1 | In the Member State concerned months | 42 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 42 |