Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
FLEX
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.
1 other identifier
interventional
1,861
27 countries
113
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2004
Longer than P75 for phase_3
113 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2004
CompletedFirst Submitted
Initial submission to the registry
September 7, 2005
CompletedFirst Posted
Study publicly available on registry
September 8, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2007
CompletedResults Posted
Study results publicly available
October 4, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2012
CompletedJune 25, 2014
June 1, 2014
2.7 years
September 7, 2005
August 24, 2011
June 13, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival Time (OS)
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
Secondary Outcomes (7)
Progression-free Survival Time
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
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
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
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
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
- +2 more secondary outcomes
Study Arms (2)
Cetuximab plus chemotherapy
EXPERIMENTALcetuximab + cisplatin + vinorelbine
Chemotherapy alone
ACTIVE COMPARATORcisplatin + vinorelbine alone
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (118)
Research Site
Buenos Aires, Argentina
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Córdoba, 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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Vienna, Austria
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Brussels, Belgium
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Charleroi, Belgium
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Liège, Belgium
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Porto Alegre, Brazil
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São Paulo, Brazil
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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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Antofagasta, Chile
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Santiago, Chile
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Brno, Czechia
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Ostrava, Czechia
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Pilsen, Czechia
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Prague, Czechia
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Brest, France
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Caen, France
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Grenoble, France
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Marseille, France
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Paris, France
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Poitiers, France
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Rennes, France
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Rouen, France
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Strasbourg, France
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Augsburg, Germany
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Berlin, Germany
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Cologne, Germany
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Essen, Germany
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Freiburg im Breisgau, Germany
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Gauting, Germany
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Göttingen, Germany
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Großhansdorf, Germany
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Halle-Dölau, Germany
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Hamburg, Germany
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Heidelberg, Germany
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Löwenstein, Germany
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Magdeburg, Germany
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Mainz, Germany
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München, Germany
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Stralsund, Germany
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Wuppertal, Germany
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Honh Kong, Hong Kong
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Budapest, Hungary
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Nyiregyháza, Hungary
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Székesfehérvár, Hungary
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Szombathely, Hungary
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Törökbálint, Hungary
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Zalegerzeg-Pózva, Hungary
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Dublin, Ireland
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Bologna, Italy
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Carpi, Italy
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Milan, Italy
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Rome, Italy
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Rozzano-Milano, Italy
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Treviglio, Italy
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Mexico City, Mexico
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Monterrey, Mexico
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Amsterdam, Netherlands
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Nieuwegeln, Netherlands
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Zwolle, Netherlands
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Bydgoszcz, Poland
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Olsztyn, Poland
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Otwock, Poland
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Posnan, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Moscow, Russia
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Saint Petersburg, Russia
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Singapore, Singapore
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Banská Bystrica, Slovakia
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Bratislava, Slovakia
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Nitra-Zobor, Slovakia
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Poprad, Slovakia
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Seoul, South Korea
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Barakaldo (Bilbao), Spain
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Barcelona, Spain
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Donostia / San Sebastian, Spain
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Elche Alicante, Spain
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Granollers, Spain
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Madrid, Spain
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Pamplona, Spain
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Pontevedra, Spain
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Santander, Spain
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Terrassa, Spain
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Valencia, Spain
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Stockholm, Sweden
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Uppsala, Sweden
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Bern, Switzerland
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Thun, Switzerland
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Zurich, Switzerland
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Taipei, Tao Yuan County, Taiwan
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Taipei, Taiwan
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Ankara, Turkey (Türkiye)
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Dnipropetrovsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Lviv, Ukraine
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Poltava, Ukraine
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Sumy, Ukraine
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Ternopil, Ukraine
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Uzhhorod, Ukraine
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Aberdeen, United Kingdom
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Bristol, United Kingdom
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Edinburgh, United Kingdom
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Leicester, United Kingdom
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London, United Kingdom
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Newcastle upon Tyne, United Kingdom
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Poole, United Kingdom
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Sutton, United Kingdom
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Wolverhampton, United Kingdom
Related Publications (5)
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.
PMID: 19410716RESULTPirker 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.
PMID: 22498112DERIVEDPirker 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.
PMID: 22056021DERIVEDO'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.
PMID: 21782507DERIVEDGatzemeier 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.
PMID: 21169060DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Merck KGaA Communication Center
- Organization
- Merck KGaA
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Pirker, Professor
Universitätsklinik für Innere Medizin I, Wien
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 7, 2005
First Posted
September 8, 2005
Study Start
October 1, 2004
Primary Completion
July 1, 2007
Study Completion
May 1, 2012
Last Updated
June 25, 2014
Results First Posted
October 4, 2011
Record last verified: 2014-06