Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX) (FLEX)
13. juni 2014 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
1861
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
-
Buenos Aires, Argentina
- Research Site
-
Cordoba, Argentina
- Research Site
-
-
-
-
-
Adelaide, Australien
- Research Site
-
Melbourne, Australien
- Research Site
-
Randwick, Australien
- Research Site
-
Sydney, Australien
- Research Site
-
Wodonga, Australien
- Research Site
-
-
-
-
-
Bruxelles, Belgien
- Research Site
-
Charleroi, Belgien
- Research Site
-
Liège, Belgien
- Research Site
-
-
-
-
-
Porto Alegre, Brasilien
- Research Site
-
Sao Paulo, Brasilien
- Research Site
-
-
-
-
-
Pleven, Bulgarien
- Research Site
-
Sofia, Bulgarien
- Research Site
-
Stara Zagora, Bulgarien
- Research Site
-
Veliko Tarnovo, Bulgarien
- Research Site
-
-
-
-
-
Antofagasta, Chile
- Research Site
-
Santiago de Chile, Chile
- Research Site
-
-
-
-
-
Moscow, Den Russiske Føderation
- Research Site
-
St. Petersburg, Den Russiske Føderation
- Research Site
-
-
-
-
-
Aberdeen, Det Forenede Kongerige
- Research Site
-
Bristol, Det Forenede Kongerige
- Research Site
-
Edinburgh, Det Forenede Kongerige
- Research Site
-
Leicester, Det Forenede Kongerige
- Research Site
-
London, Det Forenede Kongerige
- Research Site
-
Newcastle upon Tyne, Det Forenede Kongerige
- Research Site
-
Poole, Det Forenede Kongerige
- Research Site
-
Sutton, Det Forenede Kongerige
- Research Site
-
Wolverhampton, Det Forenede Kongerige
- Research Site
-
-
-
-
-
Brest, Frankrig
- Research Site
-
Caen, Frankrig
- Research Site
-
Grenoble, Frankrig
- Research Site
-
Marseille, Frankrig
- Research Site
-
Paris, Frankrig
- Research Site
-
Poitiers, Frankrig
- Research Site
-
Rennes, Frankrig
- Research Site
-
Rouen, Frankrig
- Research Site
-
Strasbourg, Frankrig
- Research Site
-
-
-
-
-
Amsterdam, Holland
- Research Site
-
Nieuwegeln, Holland
- Research Site
-
Zwolle, Holland
- Research Site
-
-
-
-
-
Honh Kong, Hong Kong
- Research Site
-
-
-
-
-
Dublin, Irland
- Research Site
-
-
-
-
-
Bologna, Italien
- Research Site
-
Carpi, Italien
- Research Site
-
Milano, Italien
- Research Site
-
Rome, Italien
- Research Site
-
Rozzano-Milano, Italien
- Research Site
-
Treviglio, Italien
- Research Site
-
-
-
-
-
Ankara, Kalkun
- Research Site
-
-
-
-
-
Seoul, Korea, Republikken
- Research Site
-
-
-
-
-
Mexico-City, Mexico
- Research Site
-
Monterrey, Mexico
- Research Site
-
-
-
-
-
Bydgoszcz, Polen
- Research Site
-
Olsztyn, Polen
- Research Site
-
Otwock, Polen
- Research Site
-
Posnan, Polen
- Research Site
-
Warszawa, Polen
- Research Site
-
Wroclaw, Polen
- Research Site
-
-
-
-
-
Bern, Schweiz
- Research Site
-
Thun, Schweiz
- Research Site
-
Zürich, Schweiz
- Research Site
-
-
-
-
-
Singapore, Singapore
- Research Site
-
-
-
-
-
Banska Bystrica, Slovakiet
- Research Site
-
Bratislava, Slovakiet
- Research Site
-
Nitra-Zobor, Slovakiet
- Research Site
-
Poprad, Slovakiet
- Research Site
-
-
-
-
-
Barakaldo (Bilbao), Spanien
- Research Site
-
Barcelona, Spanien
- Research Site
-
Elche Alicante, Spanien
- Research Site
-
Granollers, Spanien
- Research Site
-
Madrid, Spanien
- Research Site
-
Pamplona, Spanien
- Research Site
-
Pontevedra, Spanien
- Research Site
-
San Sebastian, Spanien
- Research Site
-
Santander, Spanien
- Research Site
-
Terrassa, Spanien
- Research Site
-
Valencia, Spanien
- Research Site
-
-
-
-
-
Stockholm, Sverige
- Research Site
-
Uppsala, Sverige
- Research Site
-
-
-
-
-
Taipei, Taiwan
- Research Site
-
-
Tao Yuan County
-
Taipei, Tao Yuan County, Taiwan
- Research Site
-
-
-
-
-
Brno, Tjekkiet
- Research Site
-
Ostrava, Tjekkiet
- Research Site
-
Pilsen, Tjekkiet
- Research Site
-
Praha, Tjekkiet
- Research Site
-
-
-
-
-
Augsburg, Tyskland
- Research Site
-
Berlin, Tyskland
- Research Site
-
Essen, Tyskland
- Research Site
-
Freiburg, Tyskland
- Research Site
-
Gauting, Tyskland
- Research Site
-
Großhansdorf, Tyskland
- Research Site
-
Göttingen, Tyskland
- Research Site
-
Halle-Dölau, Tyskland
- Research Site
-
Hamburg, Tyskland
- Research Site
-
Heidelberg, Tyskland
- Research Site
-
Köln, Tyskland
- Research Site
-
Löwenstein, Tyskland
- Research Site
-
Magdeburg, Tyskland
- Research Site
-
Mainz, Tyskland
- Research Site
-
München, Tyskland
- Research Site
-
Stralsund, Tyskland
- Research Site
-
Wuppertal, Tyskland
- Research Site
-
-
-
-
-
Dnipropetrovsk, Ukraine
- Research Site
-
Kharkiv, Ukraine
- Research Site
-
Kyiv, Ukraine
- Research Site
-
Lviv, Ukraine
- Research Site
-
Poltava, Ukraine
- Research Site
-
Sumy, Ukraine
- Research Site
-
Ternopol, Ukraine
- Research Site
-
Uzhgorod, Ukraine
- Research Site
-
-
-
-
-
Budapest, Ungarn
- Research Site
-
Nyiregyháza, Ungarn
- Research Site
-
Szombathely, Ungarn
- Research Site
-
Székesfehérvár, Ungarn
- Research Site
-
Torokbalint, Ungarn
- Research Site
-
Zalegerzeg-Pózva, Ungarn
- Research Site
-
-
-
-
-
Wien, Østrig
- Research Site
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Cetuximab plus chemotherapy
cetuximab + cisplatin + vinorelbine
|
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.
|
|
Aktiv komparator: Chemotherapy alone
cisplatin + vinorelbine alone
|
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.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall Survival Time (OS)
Tidsramme: 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
|
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.
|
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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression-free Survival Time
Tidsramme: 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
|
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
|
|
Best Overall Response Rate
Tidsramme: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
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).
|
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
|
Disease Control Rate
Tidsramme: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
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).
|
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
|
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Tidsramme: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
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.
|
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
|
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Tidsramme: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
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.
|
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
|
|
A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
Tidsramme: Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
|
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.
|
Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
|
|
Safety - Number of Patients Experiencing Any Adverse Event
Tidsramme: 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
|
Please refer to Adverse Events section for further details
|
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
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Robert Pirker, Professor, Universitätsklinik für Innere Medizin I, Wien
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. oktober 2004
Primær færdiggørelse (Faktiske)
1. juli 2007
Studieafslutning (Faktiske)
1. maj 2012
Datoer for studieregistrering
Først indsendt
7. september 2005
Først indsendt, der opfyldte QC-kriterier
7. september 2005
Først opslået (Skøn)
8. september 2005
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
25. juni 2014
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
13. juni 2014
Sidst verificeret
1. juni 2014
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Luftvejssygdomme
- Neoplasmer
- Lungesygdomme
- Neoplasmer efter sted
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Lungeneoplasmer
- Karcinom, ikke-småcellet lunge
- Molekylære mekanismer for farmakologisk virkning
- Antineoplastiske midler
- Tubulin modulatorer
- Antimitotiske midler
- Mitose modulatorer
- Antineoplastiske midler, fytogene
- Antineoplastiske midler, immunologiske
- Cisplatin
- Vinorelbin
- Cetuximab
Andre undersøgelses-id-numre
- EMR 62202-046
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .