E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscle-invasive bladder cancer |
Cáncer de vejiga músculo-invasivo. |
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E.1.1.1 | Medical condition in easily understood language |
Muscle-invasive bladder cancer refers to cancer that has spread into the muscle wall of bladder. |
Cáncer de vejiga músculo-invasivo se refiere a cáncer que se ha extendido a la pared muscular de la vejiga. |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022877 |
E.1.2 | Term | Invasive bladder cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 adjuvant MPDL3280A treatment in patients with programmed death ligand 1 (PD L1) selected muscle invasive bladder cancer (MIBC), as measured by disease-free survival (DFS) |
Evaluar la eficacia de MPDL3280A como tratamiento adyuvante en pacientes con cáncer de vejiga músculo-invasivo (CVMI), seleccionados por PD- L1, basándose en la supervivencia libre de enfermedad (SLE). |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the efficacy of adjuvant MPDL3280A treatment, as measured by overall survival (OS), disease-specific survival (DSS) and distant metastasis-free survival (DMFS) ? To evaluate the safety and tolerability of MPDL3280A in the adjuvant setting ? To evaluate the incidence of anti-therapeutic antibodies (ATAs) against MPDL3280A and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy ? To characterize the pharmacokinetics of MPDL32820A ? To assess health status as measured by the EuroQol 5-dimension, 5-level version (EQ-5D-5L) questionnaire |
- Evaluar la eficacia de MPDL3280A como tratamiento adyuvante, basándose en la supervivencia global (SG), en la supervivencia específica para la enfermedad (SEE) y en la supervivencia libre de metástasis a distancia (SLMD). - Evaluar la seguridad y tolerancia de MPDL3280A en el entorno adyuvante. - Evaluar la incidencia de anticuerpos antiterapéuticos (ATA) contra MPDL3280A e investigar la relación potencial de la inmunogenicidad con la farmacocinética, seguridad y eficacia. - Definir la farmacocinética de MPDL32820A. - Evaluar el estado de salud del paciente, basándose en el cuestionario EuroQol de 5 dimensiones, versión de 5 niveles (EQ-5D-5L). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >=18 years - Histologically or cytologically confirmed muscle-invasive transitional cell carcinoma (TCC) (also termed urothelial carcinoma [UC]) of the bladder (excluding TCC of renal pelvis, ureters, or urethra) - Tumor Nodes Metastasis (TNM) classification at pathological examination of cystectomy specimen - For patients treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-T4a or ypN+; For patients not treated with prior neoadjuvant chemotherapy: tumor stage of pT3-T4a or pN+ - Cystectomy with lymph node dissection - MIBC with a PD-L1 immunohistochemistry (IHC) score of IC2/3 prospectively determined on the cystectomy tumor specimens by a central laboratory - Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 6 weeks prior to randomization - Full recovery from cystectomy within 12 weeks following surgery - Eastern Cooperative Oncology Group performance status score of <=2 - Life expectancy >=12 weeks - Adequate hematologic and end-organ function - For women who are not postmenopausal (>=12 months of non?therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 90 days after the last dose of study drug |
- Tener >=18 años de edad. - Presentar CCT (también llamado CU) de vejiga (exceptuando CCT de pelvis renal, uréteres y uretra) músculo-invasivo, confirmado histológica o citológicamente. - Clasificación TNM determinado en el examen histopatológico de la muestra de cistectomía, debe ser el siguiente: ypT2-T4a o ypN+ en los pacientes tratados previamente con quimioterapia neoadyuvante, pT3-T4a o pN+ en los pacientes que no han recibido previamente quimioterapia neoadyuvante. - Cistectomía con disección de ganglios linfáticos. - CVMI con puntuación IHC para PD-L1 de IC2/3, determinada prospectivamente por el laboratorio central en muestras de tumor de la cistectomía. - Ausencia de enfermedad residual y de metástasis, confirmada por un resultado negativo en la tomografía computarizada (TAC) o resonancia magnética (RM) de pelvis, abdomen y tórax realizada en el período basal, como máximo 6 semanas antes de la randomización. - Recuperación completa de la cistectomía en las 12 semanas siguientes a la intervención quirúrgica. - Estado funcional ECOG >=2. - Esperanza de vida >=12 semanas. - Función hematológica y de órganos diana adecuada. - Las mujeres que no estén en fase postmenopáusica (es decir, sin amenorrea no inducida terapéuticamente desde hace >=12 meses) o que no estén esterilizadas quirúrgicamente (es decir, a las que no se les han extirpado los ovarios y/o el útero) deben comprometerse a practicar la abstinencia sexual o a utilizar uno o varios métodos anticonceptivos combinados que tengan una tasa de fallos anual <1%, durante el período de tratamiento y, como mínimo, hasta 90 días después de que reciban la última dosis del fármaco del estudio. |
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E.4 | Principal exclusion criteria |
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment - Adjuvant chemotherapy or radiation therapy for UC following cystectomy - Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment - Malignancies other than MIBC within 5 years prior to Cycle 1, Day 1 - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Tested Positive for HIV - Patients with active hepatitis B virus and tuberculosis - Prior allogeneic stem cell or solid organ transplant - Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina - Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies |
- Haber recibido cualquier terapia aprobada para el cáncer, incluyendo quimioterapia u hormonoterapia, en las 3 semanas previas al inicio del tratamiento del estudio. - Quimioterapia o radioterapia adyuvante para CU tras cistectomía. - Tratamiento con cualquier otro agente en investigación o participación en otro ensayo clínico con intención terapéutica en los 28 días previos a la inclusión en el estudio. - Neoplasias malignas distintas de CVMI en los 5 años previos al día 1 del ciclo 1. - Antecedentes de reacciones alérgicas, anafilácticas u otras reacciones de hipersensibidad graves a anticuerpos quiméricos o humanizados o a proteínas de fusión. - Antecedentes de enfermedades autoinmunes. - Antecedentes de fibrosis pulmonar idiopática, neumonía organizada, neumonitis inducida por fármacos, neumonitis idiopática o evidencia de neumonitis activa en el TAC de tórax realizado en el período de selección. - Resultado positivo en la prueba del VIH. - Pacientes con hepatitis B activa y tuberculosis. - Trasplante alogénico de células madre o de órganos sólidos realizado previamente. - Enfermedades cardiovasculares significativas, tales como cardiopatías de clase II o superior de la New York Heart Association, infarto de miocardio en los 3 meses previos, arritmias inestables o angina de pecho inestable. - Procedimientos de cirugía mayor que no sean con fines diagnósticos en los 28 días previos al día 1 del ciclo 1 o que previsiblemente sean necesarios en el transcurso del estudio. - Tratamiento previo con agonistas de CD137 o inhibidores de puntos de control inmunitarios, incluyendo anticuerpos terapéuticos anti-CD40, anti-CTLA-4, anti-PD-1 y anti-PD-L1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-assessed DFS |
SLP evaluada por el Investigador. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 6 years |
Hasta 6 años. |
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E.5.2 | Secondary end point(s) |
1. OS 2. DSS 3. DMFS 4. Incidence of adverse events 5. Changes in vital signs and clinical laboratory results 6. Incidence of ATA response to MPDL3280A and potential correlation with PK, pharmacodynamic, safety, and efficacy parameters 7. Maximum observed serum MPDL3280A concentration (Cmax) 8. Minimum observed serum MPDL3280A concentration (Cmin) 9. EQ-5D-5L |
1. SG 2. SEE 3. SLMD 4. Indicencia de acontecimientos adversos. 5. Cambios en las constantes vitales y los resultados de las pruebas de laboratorio clínico. 6. Incidencia de respuesta de ATA contra MPDL3280A y correlación potencial con los parámetros FC, farmacodinámicos, de seguridad y eficacia. 7. Concentración sérica mínima (Cmin) observada de MPDL3280A . 8. Concentración sérica máxima (Cmax) observada de MPDL3280A. 9. EQ-5D-Dl. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to 6 years 6. Day 1 of Cycles 1, 2, 3, 8 and every 8 cycles starting Cycle 8 until 120 days after the last dose of MDPL3280A and at treatment discontinuation visit 7. Day 1 of Cycle 1 8. Day 1 of Cycles 1, 2, 3, 8 and every 8 cycles starting Cycle 8 until 120 days after the last dose of MDPL3280A and at treatment discontinuation visit 9. Up to 6 years |
1-5. Hasta 6 años. 6. Día 1 de los Ciclos 1, 2, 3, 8 y cada 8 ciclos empezando en el Ciclo 8 hasta 120 días tras la última dosis de MPDL3280A y en la visita de discontinuación de tratamiento. 7. Día 1 del Ciclo 1. 8. Día 1 de los Ciclos 1, 2, 3, 8 y cada 8 ciclos empezando en el Ciclo 8 hasta 120 días tras la última dosis de MPDL3280A y en la visita de discontinuación de tratamiento. 9. Hasta 6 años. |
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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 | 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 | 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 | 10 |
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 |
Belarus |
Belgium |
Canada |
Czech Republic |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Serbia |
Spain |
Switzerland |
Taiwan |
Turkey |
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 the study as planned will occur when the required number of events for the final analysis of OS has occurred |
La terminación del estudio tendrá lugar, según lo previsto, cuando se haya alcanzado el número requerido de acontecimientos para el análisis final de la SG. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |