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 duration of progression-free survival of MetMAb + paclitaxel + platinum (cisplatin or carboplatin) relative to placebo + paclitaxel + platinum in all enrolled patients and in the subgroup of patients with Met diagnostic?positive tumors |
Evaluar la duración de la supervivencia libre de progresión de MetMAb + paclitaxel + platino (cisplatino o carboplatino) en comparación con placebo + paclitaxel + platino en todos los subgrupos de pacientes con tumores diagnosticados Met positivos |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the duration of survival in patients who receive paclitaxel + platinum (cisplatin or carboplatin) MetMAb relative to placebo+ platinum (cisplatin or carboplatin) in all patients and in those with Met diagnostic?positive squamous NSCLC ? To evaluate the overall response rate in patients who receive paclitaxel + platinum (cisplatin or carboplatin) MetMAb relative to placebo+ platinum (cisplatin or carboplatin) in all patients and in those with Met diagnostic?positive squamous NSCLC ? To evaluate the safety and tolerability of MetMAb in patients who receive paclitaxel + platinum (cisplatin or carboplatin) MetMAb relative to placebo+ platinum (cisplatin or carboplatin) in all patients and in those with Met diagnostic?positive squamous NSCLC ? To describe the pharmacokinetics (PK) of MetMAb when given with paclitaxel and platinum ? To evaluate the possible effect of MetMAb on the PK of paclitaxel and platinum ? To evaluate potential immune responses to MetMAb |
Evaluar la duración de supervivencia en paciente tratados con MetMAb + paclitaxel + platino (cisplatino o carboplatino) en comparación con placebo + paclitaxel + platino, en todos los pacientes y en aquellos con CPNM epidermoide Met-positivo Evaluar la la tasa de respuestas globales (TRG) en pacientes tratados con MetMAb + paclitaxel + platino (cisplatino o carboplatino) en comparación con placebo + paclitaxel + platino, en todos los pacientes y en aquellos con CPNM epidermoide Met-positivo Evaluar la seguridad y tolerabilidad de MetMAb en pacientes tratados con MetMAb + paclitaxel + platino en comparación con placebo + paclitaxel + platino, en todos los pacientes y en aquellos con CPNM epidermoide Met-positivo Describir la farmacocinética (FC) de MetMAb cuando se administra con paclitaxel y platino Evaluar el posible efecto de MetMAb sobre la FC de paclitaxel y platino Evaluar la potencial respuesta inmune 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 IV NSCLC tumors of squamous histology (Stage IIIB NSCLC eligible only if not amenable to definitive surgery or radiation therapy) Patients with stable, treated brain metastases are eligible as long as there is no evidence of progression after treatment and no ongoing requirement for dexamethasone or other corticosteroid treatment. ? 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 epidermoide en estadio IIIB o en estadio IV confirmado por histología o citología. Los pacientes con CPNM en estadio IIIB solo son elegibles si su enfermedad no es susceptible de cirugía o radioterapia definitivas. Los pacientes con metástasis cerebrales estables tratadas serán elegibles siempre que no tengan pruebas de progresión después del tratamiento y que no necesiten continuar recibiendo dexametasona u otro tratamiento con corticosteroides. 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 Utilizar un método anticonceptivo adecuado, 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 squamous NSCLC ? NSCLC with histology classified as adenocarcinoma, large cell, mixed adenosquamous, or NSCLC not otherwise specified (NOS) ? Prior exposure to experimental treatment targeting either the HGF or Met pathway ? Tumors confirmed to have EGFR activating mutations who are suitable for anti-EGFR therapy ? Uncontrolled brain metastases and treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1 ? 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, carboplatin, or paclitaxel |
Tratamiento sistémico previo para el CPNM epidermoide en estadio IIIB o IV CPNM con histología clasificada como adenocarcinoma, macrocítica o adenoepidermoide mixta, o con CPNM sin especificar 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 Metástasis cerebrales no controladas y tratamiento mediante resección quirúrgica o biopsia cerebral en las 4 semanas previas al día 1 del ciclo 1 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 concentraciones séricas bajas 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, carboplatino o paclitaxel |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Progression-free survival (PFS) |
Supervivencia libre de progresión (SLP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be evaluated when 44 investigator-assessed PFS events in patients with Met diagnostic-positive tumors and 88 PFS events in the ITT population have occurred. |
Para evaluar el criterio de valoración principal, se hará un seguimiento de los pacientes hasta el momento en que se observen al menos 44 episodios de SLP evaluados por el investigador en pacientes con tumores Met-positivos y 88 episodios de SLP 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 and potential antibodies against MetMAb ? 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 y la incidencia de ATA contra MetMAb Resultados clínicos de laboratorio y otros signos vitales Farmacocinética de todos los componentes 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 hasta que 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, niveles séricos e incidencia de ATA frente a 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 Carboplatino |
MetMAb IN COMBINATION WITH PACLITAXEL + CISPLATIN OR CARBOPLATIN |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
France |
Germany |
Israel |
Italy |
Latvia |
Spain |
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 44 investigator-assessed PFS events in patients with Met diagnostic-positive tumors and 88 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. |
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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 | 24 |
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 | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |