E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
NON?SMALL CELL LUNG CANCER |
CÁNCER DE PULMÓN NO MICROCÍTICO |
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E.1.1.1 | Medical condition in easily understood language |
NON?SMALL CELL LUNG CANCER |
CÁNCER DE PULMÓN NO MICROCÍTICO |
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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 | LLT |
E.1.2 | Classification code | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
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 16 cycles of atezolizumab treatment compared with best supportive care as measured by disease-free survival (DFS) as assessed by the investigator. |
Evaluar la eficacia de 16 ciclos de tratamiento con atezolizumab en comparación con el tratamiento de soporte óptimo (TSO), determinada mediante la supervivencia sin enfermedad (SSE) conforme a la evaluación del investigador. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of 16 cycles of atezolizumab treatment compared with BSC as measured by OS |
Evaluar la eficacia de 16 ciclos de tratamiento con atezolizumab en comparación con el TSO, determinada mediante la SG. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Tumor PD-L1 expression of TC3 or IC3, as determined by an IHC assay performed by a central laboratory on a resected tumor tissue previously obtained at screening. A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or a minimum of 15 unstained, freshly cut, serial sections from an FFPE resected tumor specimen is required for participation in this study. This specimen must be accompanied by the associated pathology report. ?ECOG performance status of 0 or 1 ?Histological or cytological diagnosis of Stage IB (tumors ? 4 cm)?IIIA (T2?3 N0, T1?3 N1, T1-3 N2) NSCLC ?Eligibility to receive a cisplatin-based chemotherapy regimen ?For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use 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 |
- Expresión de PD-L1 en el tumor de CT3 o CI3, determinada mediante un análisis de IHQ realizado en un laboratorio central con tejido tumoral resecado obtenido anteriormente en la visita de selección. Para participar en este estudio se requiere una muestra tumoral representativa fijada con formol e incluida en parafina (FFIP) en un bloque de parafina (de elección) o un mínimo de 15 extensiones seriadas, de obtención reciente y sin teñir procedentes de una muestra de tumor resecado FFIP. Esta muestra deberá ir acompañada del informe anatomopatologico correspondiente. - Estado funcional del ECOG de 0 o 1. - Diagnóstico histológico o citológico de CPNM en estadio IB (tumores ? 4 cm)-IIIA (T2-3 N0, T1-3 N1, T1-3 N2) - Elegibilidad para recibir una pauta de quimioterapia basada en cisplatino. - Mujeres en edad fértil: compromiso de mantener la abstinencia (abstenerse de relaciones heterosexuales) o de utilizar uno o varios métodos anticonceptivos con un índice de fallos <1% al año durante el período de tratamiento y durante al menos 90 días después de la última dosis del fármaco del estudio |
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E.4 | Principal exclusion criteria |
? Pregnant and lactating women ?Treatment with prior systemic chemotherapy at any time Methotrexate given in low doses for non-malignant conditions with the last dose at least 14 days prior to date of enrollment will be allowed. Other low-dose chemotherapeutics for non-malignant conditions will be considered after discussion with and approval by the Medical Monitor ?Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years before enrollment ?Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment ?Known sensitivity to any component of the chemotherapy regimen the patient will be assigned to, or to mannitol ?Prior treatment with an anti?PD-1, anti?PD-L1, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) |
- Mujeres embarazadas o en periodo de lactancia. - Tratamiento previo con quimioterapia sistémica en cualquier momento. Se permitirá la administración de metotrexato en dosis bajas por enfermedades no neoplásicas siempre que la última dosis se haya administrado al menos 14 días antes de la fecha de inclusión. La administración de otros quimioterapicos en dosis bajas por enfermedades no neoplásicas se tendrá en cuenta tras consultar al monitor médico y obtener su aprobación. - Hormonoterapia antineoplásica o radioterapia como tratamiento previo del cáncer en los 5 años previos a la inclusión. - Tratamiento con otros fármacos en investigación o participación en otro estudio clínico con intención terapéutica en los 28 días previos a la inclusión. - Hipersensibilidad conocida a cualquiera de los componentes de la pauta de quimioterapia a la que será asignado el paciente o al manitol. - Tratamiento previo con anti-PD-1, anti-PD-L1, anti-CD137 o anticuerpos contra el antígeno 4 asociado a los linfocitos T citotoxicos (como ipilimumab o cualquier otro anticuerpo o fármaco que actué específicamente sobre la coestimulación de linfocitos T o vías de puntos de control inmunológico). |
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E.5 End points |
E.5.1 | Primary end point(s) |
?DFS, defined as the time from randomization to the date of occurrence of any of the following, whichever occurs first: First recurrence of NSCLC, as determined by the investigator after an integrated assessment of radiographic data, biopsy sample results (if available), and clinical status Occurrence of new primary NSCLC, as assessed by the investigator Death from any cause |
- SSE, definida como el tiempo transcurrido entre la aleatorización y la fecha de aparición de cualquiera de las situaciones siguientes, lo que ocurra antes: Primera recidiva del CPNM, según lo determinado por el investigador tras una evaluación integrada de los datos radiológicos, los resultados de las muestras de biopsia (si procede) y el estado clínico. Aparición de un nuevo CPNM primario, conforme a lo evaluado por el investigador. Muerte por cualquier causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to E.5.1 |
Por favor, ver sección E.5.1. |
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E.5.2 | Secondary end point(s) |
?OS, defined as the time from randomization to death from any cause |
SG, definida como tiempo desde randomización hasta muerte por cualquier causa. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to E.5.2 |
Por favor, ver sección E.5.2 |
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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 | No |
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 | 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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 |
Belgium |
Canada |
China |
France |
Germany |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Taiwan |
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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The end of the study is defined as the latter of the dates of when 433 deaths have occurred in the global main study?s ITT population and 355 deaths have occurred in the Stage II?IIIA subpopulation. |
El final del estudio se define como la fecha en que se hayan producido 433 o 355 muertes en la población IT o la subpoblación en estadio II-IIIA, respectivamente, la que sea más tardía. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |