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 (CPNM) de diagnóstico positivo para Met |
|
E.1.1.1 | Medical condition in easily understood language |
Incurable lung cancer (NSCLC) |
Cáncer de pulmón incurable (CPNM) |
|
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) |
|
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) |
|
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) |
|
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 |
The primary objective of this study is to determine whether the combination of MetMAb + erlotinib is superior (in terms of overall survival) to placebo + erlotinib after standard platinum-based chemotherapy in patients with Met diagnostic?positive NSCLC. |
Determinar si la combinación de MetMAb + erlotinib es superior (en cuanto a la SG) a placebo + erlotinib tras la quimioterapia convencional b asada en el platino en pacientes con cáncer de pulmón no microcítico (CPNM) de diagnóstico positivo para Met. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows: ? To evaluate and compare the efficacy in terms of progression free survival (PFS) and overall response rate (ORR) between the two treatment groups ? To evaluate and compare the safety and tolerability of MetMAb + erlotinib versus placebo + erlotinib in patients with Met diagnostic?positive NSCLC ? To evaluate the impact of MetMAb on patient-reported outcome (PRO) measures of quality of life ? To evaluate the pharmacokinetics of MetMAb ? To evaluate serum levels and incidence of anti-therapeutic antibodies (ATAs) against MetMAb and to explore the potential relationship of the immunogenicity response with pharmacokinetics, safety, and efficacy |
Los objetivos secundarios de este estudio son: * Evaluar y comparar la eficacia en cuanto a la supervivencia sin progresión (SSP) y la tasa de respuesta objetiva (TRO) entre los dos grupos de tratamiento. * Evaluar y comparar la seguridad y la tolerabilidad de MetMAb + erlotinib frente a placebo + erlotinib en pacientes con CPNM de diagnóstico positivo para Met. * Evaluar el efecto de MetMAb sobre los criterios de valoración de la calidad de vida basados en resultados comunicados por los pacientes (RCPP). * Evaluar la farmacocinética de MetMAb. *Evaluar las concentraciones séricas y la incidencia de anticuerpos antiterapéuticos (ATA) contra MetMAb e investigar la posible relación de la respuesta de inmunogenia con la farmacocinética, la seguridad y la eficacia. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MetMAb STUDY OAM4971g OAM4971g (DNA Substudy), 11 July 2011
Objective: The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area |
SUBESTUDIO DE DEPÓSITO DE ADN ASOCIADO CON EL ESTUDIO DE MetMAb OAM4971gOAM4971g (Subestudio de DNA), 11 de Julio de 2011 Objetivo: El objetivo principal de este estudio es realizar análisis exploratorios para generar hipótesis que identifiquen los genes asociados a la respuesta al tratamiento, la toxicidad o el riesgo de enfermedad. Si se identifican dichas hipótesis genéticas, podrán contrastarse en futuros estudios clínicos dentro de este campo terapéutico |
|
E.3 | Principal inclusion criteria |
? Signed, written informed consent ? Male or female, 18 years of age or older ? ECOG performance status of 0?1 ? Stage IIIb/IV NSCLC ? Tumor sample to be centrally tested for Met and EGFR (tumor results must be Met diagnostic-positive) ? Prior treatment with at least one platinum-based line of treatment (in metastatic stage) and no more than one additional line of chemotherapy treatment |
? Consentimiento informado por escrito firmado. ? Hombres o mujeres de 18 años de edad o más. ? Pacientes con una capacidad funcional del ECOG de 0?1 ? Tumor CPNM en estadio IIIb/IV ? Muestras de tumor analizadas centralmente para Met y EGFR (los resultados del tumor deben ser positivas para el diagnóstico de Met) ? Tratamiento previo con al menos una línea de tratamiento basada en el platino (en estadio metastásico) y no más de una línea adicional de quimioterapia |
|
E.4 | Principal exclusion criteria |
? More than 30 days with an EGFR inhibitor (such as gefitinib, erlotinib, cetuximab) ? Brain metastasis or spinal cord compression unless treated and stable ? Another malignancy in the past 3 years ? Life expectancy less than 12 weeks ? Abnormal granulocytes, platelets, hemoglobin ? Abnormal serum AST (SGOT), ALT (SGPT), alkaline phosphatase (ALP), bilirubin, albumin, calcium, creatinine ? Significant history of cardiac disease ? Serious active infection or other serious medical conditions ? Inflammatory eye changes ? Clinically significant gastrointestinal abnormalities ? Unable to take oral medication, need for intravenous feeding, poor absorption, or active peptic ulcer disease ? Symptomatic hypercalcemia requiring bisphosphonate therapy ? Patients known to be HIV positive ? Recent major surgery ? Pregnant or lactating women ? Women of childbearing potential or sexually active males who are not employing adequate contraception (or practicing complete abstinence) |
Más de 30 días de exposición a un fármaco inhibidor del EGFR(tales como gefitinib, erlotinib y cetuximab). Metástasis cerebrales o compresión de la médula espinal no tratadas y sin signos de enfermedad estable Antecedentes de otra neoplasia maligna en los 3 años anteriores Esperanza de vida < 12 semanas. Recuentos anormales de granulocitos, plaquetas, hemoglobina. Valores anormales en suero de AST (SGOT), ALT (SGPT), fosfatasa alcalina (FA), bilirrubina, albúmina calcio, creatinina. Antecedentes importantes de cardiopatía Infección activa grave en el momento de la aleatorización u otras enfermedades subyacentes graves. Cualquier alteración inflamatoria de la superficie ocular Alteraciones digestivas de importancia clínica Incapacidad de tomar medicación oral, necesidad de alimentación intravenosa Intervenciones quirúrgicas previas que afecten a la absorción o úlcera péptica activa Hipercalcemia sintomática que requiere el uso continuado de tratamiento con bifosfonatos. Pacientes seropositivos para el VIH Intervención de cirugía mayor Mujeres embarazadas o en período de lactancia Mujeres en edad fértil y varones sexualmente activos que no estén utilizando métodos anticonceptivos adecuados (o que no practiquen la abstinencia completa). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival |
Supervivencia Global |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis: when 363 deaths have occurred Interim analysis: when 243 deaths have occurred |
Análisis principal: cuando se hayan producido 363 fallecimientos Análisis intermedio: cuando se hayan producido 243 fallecimientos |
|
E.5.2 | Secondary end point(s) |
? Progression-free survival ? Objective response rate ? Health related quality of life ? Adverse events ? Laboratory results ? Pharmacokinetics ? Incidence of antibodies against MetMAb |
Supervivencia libre de progresión Tasa de respuesta objetiva calidad de vida relacionada con la salud Acontecimientos adversos Resultados de laboratorio Farmacocinética Incidencia de anticuerpos contra MetMAb |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary analysis: when 363 deaths have occurred Interim analysis: when 243 deaths have occurred |
Análisis principal: cuando se hayan producido 363 fallecimientos Análisis intermedio: cuando se hayan producido 243 fallecimientos |
|
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, nievles en suero e incidencia de anticuerpos antiterapéuticos (ATA) contra MetMAb |
|
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 | 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 |
Erlotinib + MetMAb vs Erlotinib + Placebo |
Erlotinib + MetMAb vs Erlotinib + Placebo |
|
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
Belgium |
Brazil |
Canada |
Chile |
China |
Croatia |
France |
Germany |
Hong Kong |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
Taiwan |
United Kingdom |
United States |
|
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
|
The study will end after the efficacy analysis takes place; this will occur when approximately 363 deaths have occurred. (Follow-up for survival will continue until all patients have either died, are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first.) |
El estudio finalizará después de que tenga lugar el análisi de eficacia; esto ocurrirá cuando hayan sucedido 363 muertes. (El seguimiento de la supervivencia continuará hasta que todos los pacientes hayan fallecido, se pierdan en el seguimiento o el promotor decida poner finalizar el ensayo, lo que ocurra primero). |
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |