Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX) (FLEX)
13 de junio de 2014 actualizado por: Merck KGaA, Darmstadt, Germany
Open, Randomized, Controlled, Multicenter Phase III Study Comparing Cisplatin/Vinorelbine Plus Cetuximab Versus Cisplatin/Vinorelbine as First-line Treatment for Patients With Epidermal Growth Factor Receptor Expressing (EGFR-expressing) Advanced NSCLC.
The purpose of this trial is to investigate the efficacy of cetuximab in combination with chemotherapy in comparison to chemotherapy alone in patients with advanced non small cell lung cancer who did not received prior chemotherapy.
Overall survival will be taken as primary measure of efficacy.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
1861
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Augsburg, Alemania
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Berlin, Alemania
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Essen, Alemania
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Freiburg, Alemania
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Gauting, Alemania
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Großhansdorf, Alemania
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Göttingen, Alemania
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Halle-Dölau, Alemania
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Hamburg, Alemania
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Heidelberg, Alemania
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Köln, Alemania
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Löwenstein, Alemania
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Magdeburg, Alemania
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Mainz, Alemania
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München, Alemania
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Stralsund, Alemania
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Wuppertal, Alemania
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Buenos Aires, Argentina
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Cordoba, Argentina
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Adelaide, Australia
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Melbourne, Australia
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Randwick, Australia
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Sydney, Australia
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Wodonga, Australia
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Wien, Austria
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Porto Alegre, Brasil
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Sao Paulo, Brasil
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Pleven, Bulgaria
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Sofia, Bulgaria
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Stara Zagora, Bulgaria
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Veliko Tarnovo, Bulgaria
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Bruxelles, Bélgica
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Charleroi, Bélgica
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Liège, Bélgica
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Antofagasta, Chile
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Santiago de Chile, Chile
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Seoul, Corea, república de
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Banska Bystrica, Eslovaquia
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Bratislava, Eslovaquia
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Nitra-Zobor, Eslovaquia
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Poprad, Eslovaquia
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Barakaldo (Bilbao), España
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Barcelona, España
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Elche Alicante, España
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Granollers, España
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Madrid, España
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Pamplona, España
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Pontevedra, España
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San Sebastian, España
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Santander, España
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Terrassa, España
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Valencia, España
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Moscow, Federación Rusa
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St. Petersburg, Federación Rusa
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Brest, Francia
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Caen, Francia
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Grenoble, Francia
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Marseille, Francia
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Paris, Francia
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Poitiers, Francia
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Rennes, Francia
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Rouen, Francia
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Strasbourg, Francia
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Honh Kong, Hong Kong
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Budapest, Hungría
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Nyiregyháza, Hungría
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Szombathely, Hungría
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Székesfehérvár, Hungría
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Torokbalint, Hungría
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Zalegerzeg-Pózva, Hungría
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Dublin, Irlanda
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Bologna, Italia
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Carpi, Italia
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Milano, Italia
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Rome, Italia
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Rozzano-Milano, Italia
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Treviglio, Italia
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Mexico-City, México
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Monterrey, México
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Ankara, Pavo
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Amsterdam, Países Bajos
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Nieuwegeln, Países Bajos
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Zwolle, Países Bajos
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Bydgoszcz, Polonia
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Olsztyn, Polonia
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Otwock, Polonia
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Posnan, Polonia
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Warszawa, Polonia
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Wroclaw, Polonia
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Aberdeen, Reino Unido
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Bristol, Reino Unido
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Edinburgh, Reino Unido
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Leicester, Reino Unido
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London, Reino Unido
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Newcastle upon Tyne, Reino Unido
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Poole, Reino Unido
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Sutton, Reino Unido
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Wolverhampton, Reino Unido
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Brno, República Checa
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Ostrava, República Checa
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Pilsen, República Checa
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Praha, República Checa
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Singapore, Singapur
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Stockholm, Suecia
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Uppsala, Suecia
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Bern, Suiza
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Thun, Suiza
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Zürich, Suiza
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Taipei, Taiwán
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Tao Yuan County
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Taipei, Tao Yuan County, Taiwán
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Dnipropetrovsk, Ucrania
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Kharkiv, Ucrania
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Kyiv, Ucrania
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Lviv, Ucrania
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Poltava, Ucrania
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Sumy, Ucrania
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Ternopol, Ucrania
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Uzhgorod, Ucrania
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Diagnosis of histologically or cytologically confirmed NSCLC, stage IIIb with documented malignant pleural effusion or stage IV
- Immunohistochemical evidence of EGFR expression on tumor tissue
- Presence of at least 1 bi-dimensionally measurable index lesion, whereby index lesions must not lie in an irradiated area
Exclusion Criteria:
- Previous exposure to monoclonal antibodies, signal transduction inhibitors or EGFR-targeting therapy
- Previous chemotherapy for NSCLC
- Documented or symptomatic brain metastasis
- Superior vena cava syndrome contra-indicating hydration
- Previous malignancy in the last 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Cetuximab plus chemotherapy
cetuximab + cisplatin + vinorelbine
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cetuximab given as an intravenous (i.v.) infusion every week (400mg/m^2 initial dose and 250mg/m^2 subsequent doses) until progressive disease (PD) + cisplatin 80mg/m^2 i.v.
infusion on day 1 of each 3-week cycle + vinorelbine 25mg/m^2 i.v.
infusion on days 1 and 8 of each 3-week cycle.
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Comparador activo: Chemotherapy alone
cisplatin + vinorelbine alone
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cisplatin 80mg/m^2 i.v.
infusion on day 1 of each 3-week cycle + vinorelbine 25mg/m^2 i.v.
infusion on days 1 and 8 of each 3-week cycle.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Survival Time (OS)
Periodo de tiempo: Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Time from randomization to death.
Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
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Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Progression-free Survival Time
Periodo de tiempo: Time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Duration from randomization until radiological progression (based on modified World Health Organisation (WHO) criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment. |
Time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Best Overall Response Rate
Periodo de tiempo: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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The best overall response rate is defined as the proportion of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria).
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Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Disease Control Rate
Periodo de tiempo: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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The disease control rate is defined as the proportion of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments (based on modified WHO criteria).
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Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Periodo de tiempo: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Mean global health status scores (EORTC QLQ-C30) against time for each treatment group.
Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation.
Higher scores indicate a better QoL.
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at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Periodo de tiempo: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group.
Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation.
Higher scores indicate a higher level of functioning.
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at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
Periodo de tiempo: Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
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Population PK analysis was conducted using non-linear mixed effects modeling (NONMEM) software, integrating the PK data from this study and the Phase II study EMR 62 202-011.
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Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
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Safety - Number of Patients Experiencing Any Adverse Event
Periodo de tiempo: time from first dose up to 30 after last dose of study treatment, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Please refer to Adverse Events section for further details
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time from first dose up to 30 after last dose of study treatment, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Robert Pirker, Professor, Universitätsklinik für Innere Medizin I, Wien
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. doi: 10.1016/S0140-6736(09)60569-9.
- Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Eberhardt WE, de Marinis F, Heeger S, Goddemeier T, O'Byrne KJ, Gatzemeier U. Prognostic factors in patients with advanced non-small cell lung cancer: data from the phase III FLEX study. Lung Cancer. 2012 Aug;77(2):376-82. doi: 10.1016/j.lungcan.2012.03.010. Epub 2012 Apr 11.
- Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, Schumacher KM, von Heydebreck A, Celik I, O'Byrne KJ. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012 Jan;13(1):33-42. doi: 10.1016/S1470-2045(11)70318-7. Epub 2011 Nov 4.
- O'Byrne KJ, Gatzemeier U, Bondarenko I, Barrios C, Eschbach C, Martens UM, Hotko Y, Kortsik C, Paz-Ares L, Pereira JR, von Pawel J, Ramlau R, Roh JK, Yu CT, Stroh C, Celik I, Schueler A, Pirker R. Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study. Lancet Oncol. 2011 Aug;12(8):795-805. doi: 10.1016/S1470-2045(11)70189-9. Epub 2011 Jul 22.
- Gatzemeier U, von Pawel J, Vynnychenko I, Zatloukal P, de Marinis F, Eberhardt WE, Paz-Ares L, Schumacher KM, Goddemeier T, O'Byrne KJ, Pirker R. First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX phase 3 study. Lancet Oncol. 2011 Jan;12(1):30-7. doi: 10.1016/S1470-2045(10)70278-3. Epub 2010 Dec 17.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de octubre de 2004
Finalización primaria (Actual)
1 de julio de 2007
Finalización del estudio (Actual)
1 de mayo de 2012
Fechas de registro del estudio
Enviado por primera vez
7 de septiembre de 2005
Primero enviado que cumplió con los criterios de control de calidad
7 de septiembre de 2005
Publicado por primera vez (Estimar)
8 de septiembre de 2005
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
25 de junio de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
13 de junio de 2014
Última verificación
1 de junio de 2014
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades de las vías respiratorias
- Neoplasias
- Enfermedades pulmonares
- Neoplasias por sitio
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Neoplasias Pulmonares
- Carcinoma de pulmón de células no pequeñas
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Agentes antineoplásicos, fitogénicos
- Agentes antineoplásicos inmunológicos
- Cisplatino
- Vinorelbina
- Cetuximab
Otros números de identificación del estudio
- EMR 62202-046
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .