Back to resultsStudy of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX) (FLEX)
Primary Purpose
Non Small Cell Lung Cancer (NSCLC)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cetuximab + cisplatin + vinorelbine
cisplatin + vinorelbine
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer (NSCLC) focused on measuring Cetuximab, Non small cell lung cancer, Lung cancer, Cisplatin/vinorelbine, Monoclonal antibody, Erbitux
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cetuximab plus chemotherapy
Chemotherapy alone
Arm Description
cetuximab + cisplatin + vinorelbine
cisplatin + vinorelbine alone
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Progression-free Survival Time
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.
Best Overall Response Rate
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).
Disease Control Rate
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).
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
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.
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
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.
A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
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.
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details
Full Information
NCT ID
NCT00148798
First Posted
September 7, 2005
Last Updated
June 13, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00148798
Brief Title
Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
Acronym
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
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer (NSCLC)
Keywords
Cetuximab, Non small cell lung cancer, Lung cancer, Cisplatin/vinorelbine, Monoclonal antibody, Erbitux
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1861 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab plus chemotherapy
Arm Type
Experimental
Arm Description
cetuximab + cisplatin + vinorelbine
Arm Title
Chemotherapy alone
Arm Type
Active Comparator
Arm Description
cisplatin + vinorelbine alone
Intervention Type
Drug
Intervention Name(s)
cetuximab + cisplatin + vinorelbine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
cisplatin + vinorelbine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Survival Time (OS)
Description
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 Frame
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 Outcome Measure Information:
Title
Progression-free Survival Time
Description
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 Frame
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
Title
Best Overall Response Rate
Description
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).
Time Frame
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Title
Disease Control Rate
Description
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).
Time Frame
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Title
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Description
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.
Time Frame
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Title
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Description
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.
Time Frame
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Title
A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
Description
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.
Time Frame
Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
Title
Safety - Number of Patients Experiencing Any Adverse Event
Description
Please refer to Adverse Events section for further details
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Pirker, Professor
Organizational Affiliation
Universitätsklinik für Innere Medizin I, Wien
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Buenos Aires
Country
Argentina
Facility Name
Research Site
City
Cordoba
Country
Argentina
Facility Name
Research Site
City
Adelaide
Country
Australia
Facility Name
Research Site
City
Melbourne
Country
Australia
Facility Name
Research Site
City
Randwick
Country
Australia
Facility Name
Research Site
City
Sydney
Country
Australia
Facility Name
Research Site
City
Wodonga
Country
Australia
Facility Name
Research Site
City
Wien
Country
Austria
Facility Name
Research Site
City
Bruxelles
Country
Belgium
Facility Name
Research Site
City
Charleroi
Country
Belgium
Facility Name
Research Site
City
Liège
Country
Belgium
Facility Name
Research Site
City
Porto Alegre
Country
Brazil
Facility Name
Research Site
City
Sao Paulo
Country
Brazil
Facility Name
Research Site
City
Pleven
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Stara Zagora
Country
Bulgaria
Facility Name
Research Site
City
Veliko Tarnovo
Country
Bulgaria
Facility Name
Research Site
City
Antofagasta
Country
Chile
Facility Name
Research Site
City
Santiago de Chile
Country
Chile
Facility Name
Research Site
City
Brno
Country
Czech Republic
Facility Name
Research Site
City
Ostrava
Country
Czech Republic
Facility Name
Research Site
City
Pilsen
Country
Czech Republic
Facility Name
Research Site
City
Praha
Country
Czech Republic
Facility Name
Research Site
City
Brest
Country
France
Facility Name
Research Site
City
Caen
Country
France
Facility Name
Research Site
City
Grenoble
Country
France
Facility Name
Research Site
City
Marseille
Country
France
Facility Name
Research Site
City
Paris
Country
France
Facility Name
Research Site
City
Poitiers
Country
France
Facility Name
Research Site
City
Rennes
Country
France
Facility Name
Research Site
City
Rouen
Country
France
Facility Name
Research Site
City
Strasbourg
Country
France
Facility Name
Research Site
City
Augsburg
Country
Germany
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Essen
Country
Germany
Facility Name
Research Site
City
Freiburg
Country
Germany
Facility Name
Research Site
City
Gauting
Country
Germany
Facility Name
Research Site
City
Großhansdorf
Country
Germany
Facility Name
Research Site
City
Göttingen
Country
Germany
Facility Name
Research Site
City
Halle-Dölau
Country
Germany
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Heidelberg
Country
Germany
Facility Name
Research Site
City
Köln
Country
Germany
Facility Name
Research Site
City
Löwenstein
Country
Germany
Facility Name
Research Site
City
Magdeburg
Country
Germany
Facility Name
Research Site
City
Mainz
Country
Germany
Facility Name
Research Site
City
München
Country
Germany
Facility Name
Research Site
City
Stralsund
Country
Germany
Facility Name
Research Site
City
Wuppertal
Country
Germany
Facility Name
Research Site
City
Honh Kong
Country
Hong Kong
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Nyiregyháza
Country
Hungary
Facility Name
Research Site
City
Szombathely
Country
Hungary
Facility Name
Research Site
City
Székesfehérvár
Country
Hungary
Facility Name
Research Site
City
Torokbalint
Country
Hungary
Facility Name
Research Site
City
Zalegerzeg-Pózva
Country
Hungary
Facility Name
Research Site
City
Dublin
Country
Ireland
Facility Name
Research Site
City
Bologna
Country
Italy
Facility Name
Research Site
City
Carpi
Country
Italy
Facility Name
Research Site
City
Milano
Country
Italy
Facility Name
Research Site
City
Rome
Country
Italy
Facility Name
Research Site
City
Rozzano-Milano
Country
Italy
Facility Name
Research Site
City
Treviglio
Country
Italy
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Mexico-City
Country
Mexico
Facility Name
Research Site
City
Monterrey
Country
Mexico
Facility Name
Research Site
City
Amsterdam
Country
Netherlands
Facility Name
Research Site
City
Nieuwegeln
Country
Netherlands
Facility Name
Research Site
City
Zwolle
Country
Netherlands
Facility Name
Research Site
City
Bydgoszcz
Country
Poland
Facility Name
Research Site
City
Olsztyn
Country
Poland
Facility Name
Research Site
City
Otwock
Country
Poland
Facility Name
Research Site
City
Posnan
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Wroclaw
Country
Poland
Facility Name
Research Site
City
Moscow
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
Country
Russian Federation
Facility Name
Research Site
City
Singapore
Country
Singapore
Facility Name
Research Site
City
Banska Bystrica
Country
Slovakia
Facility Name
Research Site
City
Bratislava
Country
Slovakia
Facility Name
Research Site
City
Nitra-Zobor
Country
Slovakia
Facility Name
Research Site
City
Poprad
Country
Slovakia
Facility Name
Research Site
City
Barakaldo (Bilbao)
Country
Spain
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Elche Alicante
Country
Spain
Facility Name
Research Site
City
Granollers
Country
Spain
Facility Name
Research Site
City
Madrid
Country
Spain
Facility Name
Research Site
City
Pamplona
Country
Spain
Facility Name
Research Site
City
Pontevedra
Country
Spain
Facility Name
Research Site
City
San Sebastian
Country
Spain
Facility Name
Research Site
City
Santander
Country
Spain
Facility Name
Research Site
City
Terrassa
Country
Spain
Facility Name
Research Site
City
Valencia
Country
Spain
Facility Name
Research Site
City
Stockholm
Country
Sweden
Facility Name
Research Site
City
Uppsala
Country
Sweden
Facility Name
Research Site
City
Bern
Country
Switzerland
Facility Name
Research Site
City
Thun
Country
Switzerland
Facility Name
Research Site
City
Zürich
Country
Switzerland
Facility Name
Research Site
City
Taipei
State/Province
Tao Yuan County
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan
Facility Name
Research Site
City
Ankara
Country
Turkey
Facility Name
Research Site
City
Dnipropetrovsk
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
Country
Ukraine
Facility Name
Research Site
City
Kyiv
Country
Ukraine
Facility Name
Research Site
City
Lviv
Country
Ukraine
Facility Name
Research Site
City
Poltava
Country
Ukraine
Facility Name
Research Site
City
Sumy
Country
Ukraine
Facility Name
Research Site
City
Ternopol
Country
Ukraine
Facility Name
Research Site
City
Uzhgorod
Country
Ukraine
Facility Name
Research Site
City
Aberdeen
Country
United Kingdom
Facility Name
Research Site
City
Bristol
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
Country
United Kingdom
Facility Name
Research Site
City
Leicester
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Newcastle upon Tyne
Country
United Kingdom
Facility Name
Research Site
City
Poole
Country
United Kingdom
Facility Name
Research Site
City
Sutton
Country
United Kingdom
Facility Name
Research Site
City
Wolverhampton
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
19410716
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.
Results Reference
result
PubMed Identifier
22498112
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.
Results Reference
derived
PubMed Identifier
22056021
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.
Results Reference
derived
PubMed Identifier
21782507
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.
Results Reference
derived
PubMed Identifier
21169060
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.
Results Reference
derived
Learn more about this trial
Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
We'll reach out to this number within 24 hrs