E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SQUAMOUS NON?SMALL CELL LUNG CANCER |
Cáncer de pulmón no microcítico escamoso. |
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E.1.1.1 | Medical condition in easily understood language |
SQUAMOUS NON?SMALL CELL LUNG CANCER |
Cáncer de pulmón no microcítico escamoso. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 in the ITT population as measured by investigator-assessed PFS according to RECIST v1.1 in each of the following two treatment comparisons: MPDL3280A + carboplatin + paclitaxel versus carboplatin + nab-paclitaxel MPDL3280A + carboplatin + nab-paclitaxel versus carboplatin + nab-paclitaxel ? To evaluate the efficacy of MPDL3280A in the PD-L1?selected population as measured by investigator-assessed PFS according to RECIST v1.1 in each of the two treatment comparisons |
- Evaluar la eficacia de MPDL3280A en la población por intención de tratamiento (IT), determinada mediante la supervivencia libre de progresión (SLP) evaluada por el investigador conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST v1.1) en cada una de las dos comparaciones entre tratamientos siguientes: MPDL3280A + carboplatino + paclitaxel frente a carboplatino + nab paclitaxel. MPDL3280A + carboplatino + nab paclitaxel frente a carboplatino + nab paclitaxel. - Evaluar la eficacia de MPDL3280A en la población seleccionada por PD L1, determinada mediante la SLP evaluada por el investigador conforme a los criterios RECIST v1.1 en cada una de las dos comparaciones entre tratamientos descritas anteriormente. |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the efficacy of MPDL3280A as measured by investigator-assessed ORR according to RECIST v1.1 in each of the two treatment comparisons ? To evaluate the efficacy of MPDL3280A as measured by OS in each of the two treatment comparisons ? To evaluate the efficacy of MPDL3280A as measured by investigator-assessed duration of response (DOR) according to RECIST v1.1 in each of the two treatment comparisons |
- Evaluar la eficacia de MPDL3280A determinada mediante la tasa de respuestas objetivas (TRO) evaluada por el investigador conforme a los criterios RECIST v1.1 en cada una de las dos comparaciones entre tratamientos. - Evaluar la eficacia de MPDL3280A determinada mediante la supervivencia global (SG) en cada una de las dos comparaciones. - Evaluar la eficacia de MPDL3280A determinada mediante la duración de la respuesta (DR) evaluada por el investigador conforme a los criterios RECIST v1.1 en cada una de las dos comparaciones entre tratamientos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? ECOG performance status of 0 or 1 ? Histologically or cytologically confirmed, Stage IV squamous NSCLC ? No prior treatment for Stage IV squamous NSCLC Patients with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with erlotinib, gefitinib, or another EGFR tyrosine kinase inhibitor (TKI) appropriate for the treatment of EGFR-mutant NSCLC. Patients with an ALK fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e. crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene. ? Patients who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy or completion of chemoradiotherapy. ? Measurable disease, as defined by RECIST v1.1 |
- Estado funcional ECOG de 0 o 1 - CPNM escamoso, confirmado mediante histología o citología, estadio IV - Ausencia de tratamiento previo para el CPNM escamoso estadio IV. Los pacientes con una mutación sensibilizadora en el gen EGFR tendrán que haber presentado progresión de la enfermedad (durante o después del tratamiento) o intolerancia al tratamiento con erlotinib, gefitinib u otro inhibidor de la tirosina quinasa (TKI) EGFR adecuado para tratar el CPNM con mutación de EGFR. Los pacientes con un oncogén de fusión ALK tendrán que haber presentado progresión de la enfermedad (durante o después del tratamiento) o intolerancia al tratamiento con uno o varios inhibidores de ALK (por ejemplo, crizotinib) adecuados para tratar el CPNM en pacientes con un oncogén de fusión ALK. -Los pacientes que hayan recibido quimioterapia neoadyuvante o adyuvante previa o quimiorradioterapia con intención curativa por enfermedad no metastásica tendrán que haber presentado un intervalo sin tratamiento de al menos 6 meses con respecto a la aleatorización desde la última quimioterapia o la finalización de la quimiorradioterapia. - Enfermedad mensurable, definida conforme a los criterios RECIST v1.1. |
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E.4 | Principal exclusion criteria |
? Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments ? Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization ? Leptomeningeal disease ? Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) ? History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins ? Positive test for HIV |
- Metástasis en el SNC activas o no tratadas, determinadas mediante TC o RM durante las evaluaciones radiológicas de selección y precedentes. - Compresión medular no tratada de forma definitiva con cirugía o radioterapia o compresión medular ya diagnosticada y tratada sin indicios de que la enfermedad haya permanecido clínicamente estable durante > 2 semanas antes de la aleatorización. - Afectación leptomeníngea. - Derrame pleural, derrame pericárdico o ascitis no controlados con necesidad de procedimientos de drenaje recurrentes (una vez al mes o con más frecuencia). - Antecedentes de reacciones alérgicas, anafilácticas o de hipersensibilidad intensas frente a proteínas de fusión o anticuerpos humanizados o quiméricos. - Resultado positivo en una prueba del VIH. |
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E.5 End points |
E.5.1 | Primary end point(s) |
? PFS, defined as the time from randomization to the first occurrence of the disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first |
- SLP, definida como el tiempo transcurrido entre la aleatorización y el primer episodio de progresión de la enfermedad, determinada por el investigador conforme a los criterios RECIST v1.1, o la muerte por cualquier causa, lo que ocurra antes. |
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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 E.5.1 |
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E.5.2 | Secondary end point(s) |
? Objective response, defined as partial response (PR) or complete response (CR) as determined by the investigator according to RECIST v1.1 ? OS, defined as the time from randomization to death from any cause ? DOR, defined as the time from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first |
- Respuesta objetiva, definida como una respuesta parcial (RP) o completa (RC) determinada por el investigador conforme a los criterios RECIST v1.1. - SG, definida como el tiempo transcurrido entre la aleatorización y la muerte por cualquier causa. - DR, definida como el tiempo transcurrido entre el primer episodio de respuesta objetiva documentada y la fecha de progresión de la enfermedad, determinada por el investigador conforme a los criterios RECIST v1.1, o la muerte por cualquier causa, lo que ocurra antes. |
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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 E.5.1 |
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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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 23 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Brazil |
Bulgaria |
Canada |
Chile |
China |
France |
Germany |
Israel |
Italy |
Japan |
Latvia |
Lithuania |
Mexico |
Netherlands |
Peru |
Portugal |
Russian Federation |
Singapore |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Ukraine |
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 study is when the required number of deaths have been observed. |
El final del estudio tendrá lugar cuando se haya observado el número exigido de muertes. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |