E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced tumor and metastastic disease |
Tumores avanzados y enfermedad metastásica. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced tumor and metastastic disease |
Tumores avanzados y enfermedad metastásica. |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046721 |
E.1.2 | Term | Urothelial carcinoma bladder stage III |
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 MPDL3280A treatment compared with chemotherapy treatment with respect to OS in patients with locally advanced or metastatic UBC who have progressed during or following a platinum-containing regimen |
Evaluar la eficacia del tratamiento con MPDL3280A en comparación con la quimioterapia con respecto a la SG en pacientes con CVU localmente avanzado o metastásico que experimentan progresión durante o después de una pauta con platino. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of MPDL3280A compared with chemotherapy with respect to anti-tumor effects as measured by ORR per investigator with use of RECIST v1.1 To evaluate the efficacy of MPDL3280A compared with chemotherapy with respect to anti-tumor effects as measured by PFS per investigator with use of RECIST v1.1 To evaluate the efficacy of MPDL3280A compared with chemotherapy with respect to anti-tumor effects as measured by duration of objective response (DOR) per RECIST v1.1 |
Evaluar la eficacia de MPDL3280A en comparación con la quimioterapia con respecto a los efectos antitumorales, basándose en la TRO determinada por el investigador aplicando los criterios RECIST v1.1 Evaluar la eficacia de MPDL3280A en comparación con la quimioterapia con respecto a los efectos antitumorales, basándose en la SSP determinada por el investigador aplicando los criterios RECIST v1.1 Evaluar la eficacia de MPDL3280A en comparación con la quimioterapia con respecto a los efectos antitumorales, basándose en la duración de la respuesta objetiva (DR) según los criterios RECIST v1.1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Age >/= 18 years ?Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra) ?Representative tumor specimens as specified by the protocol ?Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ?Life expectancy >/= 12 weeks ?Measurable disease, as defined by RECIST v1.1 ?Adequate hematologic and end organ function ?Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence |
-Edad >/= 18 años -CVU (también denominado CCT o CCU de las vías urinarias, lo que incluye pelvis renal, uréteres, vejiga urinaria y uretra) localmente avanzado o metastásico confirmado mediante examen histológico o citológico. -Disponibilidad de muestras de tumor representativas como se especifican en el protocolo. -Estado funcional del ECOG de 0 o 1. -Esperanza de vida >/= 12 semanas. -Enfermedad medible, definida con arreglo a los criterios RECIST v1.1. -Función hematológica y de órganos diana adecuada. -Progresión de la enfermedad durante o después del tratamiento con al menos una pauta que contenga platino (p. ej., GC, MVAC, CarboGem, etc.) en caso de CVU localmente avanzado metastásico inoperable o recidiva de la enfermedad. |
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E.4 | Principal exclusion criteria |
? Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment ? Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment ? Active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments ?Leptomeningeal disease ?Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome or incidental prostate cancer ?Pregnant and lactating women ?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 ?Serum albumin < 2.5 g/dL ?Positive test for HIV and/or active hepatitis B or hepatitis C or tuberculosis ?Severe infections within 4 weeks prior to Cycle 1, Day 1 ?Significant cardiovascular disease ?Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 ?Prior allogeneic stem cell or solid organ transplant ?Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 ?Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications ?Prior treatment with CD137 agonists or immune checkpoint blockade |
-Cualquier tratamiento antineoplásico aprobado, en las 3 semanas previas al comienzo del tratamiento del estudio. -Tratamiento con cualquier otro fármaco en fase de investigación o participación en otro ensayo clínico con intención terapéutica en los 28 días previos a la inclusión. -Metástasis activas o no tratadas en el SNC según lo determinado por la tomografía computarizada (TC) o la resonancia magnética (RM) durante la selección y los estudios radiológicos anteriores - Enfermedad leptomeníngea -Neoplasias malignas distintas del CVU en los 5 años previos al día 1 del ciclo 1, a excepción de aquellas con un riesgo insignificante de metástasis o muerte y tratadas con un resultado curativo previsto o cáncer de próstata localizado. -Embarazo y lactancia -Antecedentes de enfermedades autoinmunitarias - Antecedentes de fibrosis pulmonar idiopática, neumonitis inducida por fármacos, neumonía organizada, o signos de neumonitis activa en la TC de tórax realizada en la selección. -Resultado positivo en el análisis del VIH/hepatitis B activa o hepatitis C o Tuberculosis activa -Infecciones graves en las 4 semanas previas a la aleatorización --Enfermedad cardiovascular importante Procedimiento de cirugía mayor en las 4 semanas previas a la aleatorización -Pacientes con alotrasplante de células progenitoras o trasplante de órgano sólido realizado con anterioridad -Administración de una vacuna de microbios vivos atenuados en las 4 semanas previas a la aleatorización -Tratamiento previo con agonistas de CD137, anti?PD-1 o anticuerpo terapéutico anti?PD-L1 o fármacos que actúen en determinadas vías |
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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 |
every 3 months until death, loss to follow-up, or study termination by the Sponsor |
Cada 3 meses, hasta la muerte, la pérdida para el seguimiento o la terminación del estudio por el promotor |
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E.5.2 | Secondary end point(s) |
overall response rate (ORR), progression free survival (PFS), duration of response (DOR) |
Tasa de respuestas objetivas (TRO), supervivencia sin progresión (SSP), duración de la respuesta objetiva (DR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 9 weeks for 54 weeks and every 12 weeks thereafter until disease progression |
Cada 9 semanas durante 54 semanas y luego cada 12 semanas hasta la progresión de la enfermedad |
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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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Austria |
Belgium |
Bosnia and Herzegovina |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Italy |
Latvia |
Lithuania |
Mexico |
Netherlands |
Norway |
Peru |
Poland |
Portugal |
Romania |
Slovakia |
Slovenia |
Spain |
Sweden |
Switzerland |
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 is defined as the date when all patients have one of the following: ? Experienced an OS event ? Been lost to follow-up ? Withdrawn consent |
El fin del estudio se define como la fecha en la que todos los pacientes: -Hayan experimentado un episodio de SG -Se hayan perdido para el seguimiento -Hayan retirado su consentimiento |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |