E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MET DIAGNOSTIC?POSITIVE NON?SMALL CELL LUNG CANCER (NSCLC) |
Cáncer de pulmón no microcítico (NSCLC) diagnosticado Met-positivos |
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E.1.1.1 | Medical condition in easily understood language |
Incurable lung cancer (NSCLC) |
Cáncer de pulmón (NSCLC) incurable |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025048 |
E.1.2 | Term | Lung cancer non-small cell recurrent |
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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 MetMAb compared with placebo by PFS in all patients and in the subgroup of patients with Met diagnostic?positive tumors in each of two combination treatment cohorts: Cohort 1: MetMAb + bevacizumab + platinum + paclitaxel vs. placebo + bevacizumab + platinum + paclitaxel Cohort 2: MetMAb + platinum + pemetrexed vs. placebo + platinum + pemetrexed |
Evaluar la eficacia por PFS de MetMAb en comparación con placebo en todos los pacientes y en el subgrupo de pacientes con tumores diagnosticados met positivosen cada una de dos cohortes de tratamiento: Cohorte 1: MetMAb + bevacizumab + platino + paclitaxel en comparación con placebo + bevacizumab + platino + paclitaxel Cohorte 2: MetMAb + platino + pemetrexed en comparación con placebo + platino + pemetrexed |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the efficacy of MetMAb compared with placebo, as measured by OS, in each treatment cohort, in all patients and in those who have Met diagnostic?positive NSCLC ? To evaluate the efficacy of MetMAb compared with placebo, as measured by overall response rate (ORR), duration of response (DOR), and disease control rate (DCR), in each treatment cohort, in all patients and in those who have Met diagnostic?positive NSCLC ? To evaluate the safety and tolerability of MetMAb compared with placebo ? To describe the pharmacokinetics (PK) of MetMAb given in combination with bevacizumab, platinum, and paclitaxel or pemetrexed ? To evaluate the possible effect of MetMAb on the PK of bevacizumab, platinum, paclitaxel, and pemetrexed ? To evaluate potential immune responses against MetMAb |
Evaluar la eficacia de MetMAb en comparación con placebo, según lo determinado por la SG, en cada una de las dos cohortes de tratamiento descritas anteriormente, en las poblaciones por IT y Met-positiva Evaluar la eficacia de MetMAb en comparación con placebo, según lo determinado por la tasa de respuestas globales (TRO), la duración de la respuesta (DR) y la tasa de control de la enfermedad (TCE), en cada una de las dos cohortes de tratamiento descritas anteriormente, en las poblaciones por IT y Met-positiva. Evaluar la seguridad y la tolerabilidad de MetMAb en comparación con placebo Describir la farmacocinética (FC) de MetMAb cuando se administra en combinación con bevacizumab, platino y paclitaxel o pemetrexed Evaluar el posible efecto de MetMAb sobre la farmacocinética de bevacizumab, platino, paclitaxel y pemetrexed Evaluar la potencial respuesta inmune frente a MetMAb |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Written informed consent ? Male or female, 18 years of age or older ? ECOG performance status of 0 or 1 ? Stage IIIB or Stage IV NSCLC tumors of non-squamous histology (Stage IIIB eligible only if stage T4 disease not amenable to definitive surgery or radiation therapy) ? For patients who received prior adjuvant chemotherapy: a treatment free interval of at least 12 months since the last chemotherapy cycle ? Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown ? Adequate hematologic, hepatic, and renal function ? Adequate contraception, during the treatment period and for at least 90 days after the last dose of study drug, if applicable. |
Consentimiento informado por escrito Varones o mujeres de 18 o más años de edad Estado funcional del ECOG de 0 o 1 CPNM no epidermoide en estadio IIIB o IV confirmado por histología o citología (pacientes con CPNM en estadio IIIB podrán participar solo si presentan enfermedad en estadio T4 no susceptible de cirugía o radioterapia definitivas). Pacientes que hayan recibido anteriormente quimioterapia adyuvante Tejido suficiente para el análisis por IHQ central del receptor Met y análisis del EGFR si se desconoce el estado del EGFR Adecuada función hematológica, hepática y renal Adecuado método anticonceptivo, durante el período de tratamiento y durante al menos 90 días después de la última dosis de la medicación del estudio |
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E.4 | Principal exclusion criteria |
? Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC ? Mixed NSCLC histology with squamous cell predominance ? Prior exposure to experimental treatment targeting either the HGF or Met pathway ? Tumors confirmed to have EGFR activating mutations suitable for anti-EGFR therapy ? Known central nervous system (CNS) disease, other than stable, treated brain metastasis ? History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years (except for in situ cancer or basal or squamous cell skin cancer) ? Serum calcium > ULN (corrected for low serum albumin concentrations) ? Uncontrolled diabetes (fasting serum glucose level > 200 mg/dL) ? Pregnancy or lactation ? Significant history of cardiovascular disease ? Serious active infection or other serious underlying medical conditions ? Known HIV positivity ? Any major surgery, major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1, or an anticipated need for major surgery during the study ? Known sensitivity to any component of cisplatin or carboplatin ? (Patients with contraindications to bevacizumab or pemetrexed may not be included in those treatment cohorts) |
Tratamiento sistémico previo para el CPNM no epidermoide en estadio IIIB o IV Signos histológicos de CPNM mixto con predominio del tipo epidermoide Exposición previa a tratamiento experimental dirigido a la vía de HGF o Met Pacientes con tumores con mutaciones activadoras de EGFR confirmadas que sean adecuados para tratamiento anti-EGFR Enfermedad conocida del sistema nervioso central (SNC) que no sea estable y metástasis cerebrales tratadas Antecedentes de otra neoplasia maligna en los 3 años anteriores, con un intervalo sin enfermedad de < 3 años Podrán participar los pacientes con antecedentes de cáncer in situ o cáncer de piel basocelular o espinocelular. Calcio sérico > LSN (corregido respecto a unas bajas concentraciones séricas de albúmina) Diabetes no controlada, demostrada por una glucemia en ayunas 200 mg/dl Embarazo o lactancia Antecedentes importantes de enfermedad cardiovascular Infección activa grave u otras enfermedades subyacentes graves Pacientes VIH-positivos Cualquier intervención de cirugía mayor, procedimiento quirúrgico importante, biopsia abierta, pleurodesis abierta o lesión traumática significativa en los 28 días previos al día 1 del ciclo 1, o necesidad prevista de cirugía mayor durante el estudio Hipersensibilidad conocida a cualquiera de los componentes de cisplatino o carboplatino |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Progression-free survival (PFS) |
Supervivencia libre de progresión (SSP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be evaluated when 48 investigator-assessed PFS events in patients with Met diagnostic-positive tumors and 96 PFS events in the ITT population have occurred. |
El análisis de la eficacia se realizará cuando se hayan producido 48 episodios de SSP evaluados por el investigador en pacientes con tumores Met-positivos y 96 episodios de SSP en la población por IT. |
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E.5.2 | Secondary end point(s) |
? Overall survival (OS) ? Overall response rate (ORR) ? Duration of response (DOR) ? Disease control rate (DCR) ? Adverse events, including serious AEs ? Clinical laboratory results and vital signs ? Pharmacokinetics for all components of study treatments |
Supervivencia global (SG). Tasa de respuestas objetivas (TRO). Duración de la respuesta objetiva (DRO). Tasa de control de la enfermedad (TCE). Acontecimientos adversos, incluyendo los AE graves Resultados clínicos de laboratorio y signos vitales Farmacocinética de todos los pacientes de los tratamientos de estudio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Follow-up for survival will continue until all patients have either died, or are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first. |
El seguimiento de la supervivencia continuará hasta que todos los pacientes hayan fallecido o se hayan perdido para el seguimiento, o el promotor decida poner fin al ensayo, lo que ocurra antes. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, QoL, Serum levels and incidence of anti-therapeutic antibodies (ATAs) against MetMAb |
Tolerabilidad, Calidad de vida, nieveles séricos e incidencia de ATA contra MetMAb |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
MetMAb EN COMBINACIÓN CON PACLITAXEL + CISPLATINO O CARBOPLATIN |
MetMAb IN COMBINATION WITH PACLITAXEL + CISPLATIN OR CARBOPLATIN |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 33 |
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 |
Brazil |
Colombia |
France |
Germany |
Israel |
Italy |
Latvia |
Malaysia |
Mexico |
Philippines |
Portugal |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 efficacy analysis will occur when 48 investigator-assessed PFS events in patients with Met diagnostic-positive tumors and 96 PFS events in the ITT population have occurred. Follow-up for survival will continue until all patients have either died, or are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first. Depending on study outcome, patients may be allowed to continue treatment if they are deriving benefit, with continued safety follow-up. |
El análisis de la eficacia se realizará tras 48 episodios de SSP evaluados por investigador en pacientes con tumores Met-positivos y 96 episodios de SSP en la población por IT. El seguimiento continuará hasta que todos los pacientes hayan fallecido o se hayan perdido para el seguimiento, o el promotor decida poner fin al ensayo, lo que ocurra antes. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 26 |
E.8.9.2 | In all countries concerned by the trial days | 0 |