Clinical trial NCT00148798: Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer (NSCLC)
Keywords: Cetuximab
Non small cell lung cancer
Lung cancer
Cisplatin/vinorelbine
Monoclonal antibody
Erbitux
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2005-09-08
Enrollment: 1861
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival Time (OS)
timeFrame: 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:
measure: Progression-free Survival Time
timeFrame: 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
measure: Best Overall Response Rate
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
measure: Disease Control Rate
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
measure: Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
timeFrame: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
measure: Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
timeFrame: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
measure: A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
timeFrame: Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
measure: Safety - Number of Patients Experiencing Any Adverse Event
timeFrame: 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
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Adelaide
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Sydney
country: Australia
facility: Research Site
city: Wodonga
country: Australia
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Veliko Tarnovo
country: Bulgaria
facility: Research Site
city: Antofagasta
country: Chile
facility: Research Site
city: Santiago de Chile
country: Chile
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Ostrava
country: Czech Republic
facility: Research Site
city: Pilsen
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Grenoble
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Großhansdorf
country: Germany
facility: Research Site
city: Göttingen
country: Germany
facility: Research Site
city: Halle-Dölau
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Löwenstein
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Stralsund
country: Germany
facility: Research Site
city: Wuppertal
country: Germany
facility: Research Site
city: Honh Kong
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Nyiregyháza
country: Hungary
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Torokbalint
country: Hungary
facility: Research Site
city: Zalegerzeg-Pózva
country: Hungary
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Carpi
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Rozzano-Milano
country: Italy
facility: Research Site
city: Treviglio
country: Italy
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Mexico-City
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Nieuwegeln
country: Netherlands
facility: Research Site
city: Zwolle
country: Netherlands
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Otwock
country: Poland
facility: Research Site
city: Posnan
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Nitra-Zobor
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Barakaldo (Bilbao)
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Elche Alicante
country: Spain
facility: Research Site
city: Granollers
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Pontevedra
country: Spain
facility: Research Site
city: San Sebastian
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Terrassa
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Thun
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
state: Tao Yuan County
city: Taipei
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Ternopol
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Poole
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Universitätsklinik für Innere Medizin I, Wien
name: Robert Pirker, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.