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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00148798




Registration number
NCT00148798
Ethics application status
Date submitted
7/09/2005
Date registered
8/09/2005
Date last updated
25/06/2014

Titles & IDs
Public title
Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
Scientific 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.
Secondary ID [1] 0 0
EMR 62202-046
Universal Trial Number (UTN)
Trial acronym
FLEX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cetuximab + cisplatin + vinorelbine
Treatment: Drugs - cisplatin + vinorelbine

Experimental: Cetuximab plus chemotherapy - cetuximab + cisplatin + vinorelbine

Active Comparator: Chemotherapy alone - cisplatin + vinorelbine alone


Treatment: Drugs: 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.

Treatment: Drugs: cisplatin + vinorelbine
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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 [1] 0 0
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.
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
Secondary outcome [7] 0 0
Safety - Number of Patients Experiencing Any Adverse Event - Please refer to Adverse Events section for further details
Timepoint [7] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Randwick
Recruitment hospital [4] 0 0
Research Site - Sydney
Recruitment hospital [5] 0 0
Research Site - Wodonga
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment postcode(s) [5] 0 0
- Wodonga
Recruitment outside Australia
Country [1] 0 0
Argentina
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Buenos Aires
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Argentina
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Cordoba
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Charleroi
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Belgium
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Liège
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Brazil
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Porto Alegre
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Brazil
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Sao Paulo
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Bulgaria
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Pleven
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Bulgaria
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Sofia
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Bulgaria
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Stara Zagora
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Bulgaria
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Veliko Tarnovo
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Chile
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Antofagasta
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Chile
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Santiago de Chile
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Czech Republic
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Brno
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Czech Republic
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Ostrava
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Czech Republic
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Pilsen
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Czech Republic
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Praha
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France
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Brest
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France
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Caen
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France
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Grenoble
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France
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Marseille
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France
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Paris
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France
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Poitiers
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France
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Rennes
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France
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Rouen
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France
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Strasbourg
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Germany
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Augsburg
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Germany
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Berlin
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Germany
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Essen
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Germany
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Freiburg
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Germany
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Gauting
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Germany
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Großhansdorf
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Germany
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Göttingen
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Germany
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Halle-Dölau
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Köln
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Germany
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Löwenstein
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Magdeburg
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Mainz
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München
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Stralsund
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Germany
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Wuppertal
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Hong Kong
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Honh Kong
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Hungary
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Budapest
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Hungary
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Nyiregyháza
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Hungary
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Szombathely
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Hungary
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Székesfehérvár
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Hungary
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Torokbalint
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Zalegerzeg-Pózva
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Ireland
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Dublin
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Bologna
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Italy
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Carpi
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Milano
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Italy
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Rome
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Italy
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Rozzano-Milano
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Italy
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Treviglio
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Nieuwegeln
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Netherlands
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Zwolle
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Poland
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Bydgoszcz
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Olsztyn
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Otwock
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Posnan
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Warszawa
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Wroclaw
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Russian Federation
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Moscow
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Banska Bystrica
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Bratislava
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Nitra-Zobor
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Poprad
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Barcelona
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Elche Alicante
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Granollers
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Madrid
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Pamplona
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Pontevedra
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San Sebastian
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Santander
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Terrassa
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Valencia
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Stockholm
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Uppsala
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Switzerland
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Bern
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Switzerland
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Thun
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Switzerland
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Zürich
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Taiwan
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Tao Yuan County
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Taiwan
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Taipei
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Turkey
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Ankara
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Ukraine
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Dnipropetrovsk
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Poltava
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Ukraine
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Sumy
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Ukraine
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Ternopol
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Ukraine
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Uzhgorod
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United Kingdom
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Aberdeen
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United Kingdom
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Bristol
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United Kingdom
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Edinburgh
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
State/province [111] 0 0
Poole
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United Kingdom
State/province [112] 0 0
Sutton
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT00148798
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert Pirker, Professor
Address 0 0
Universitätsklinik für Innere Medizin I, Wien
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications