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Non Small Cell Lung Cancer (NSCLC)Phase 3FLEXNCT00148798

Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)

A Phase 3 study testing cetuximab + cisplatin + vinorelbine and cisplatin + vinorelbine in people with Non Small Cell Lung Cancer (NSCLC), run by Merck KGaA, Darmstadt, Germany at 118 sites in 28 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer (NSCLC)
What is being tested?
cetuximab + cisplatin + vinorelbine and cisplatin + vinorelbine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,861 participants
Where
118 sitesin 28 countries
Study dates
Oct 2004to May 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

118 sites in 28 countries.

118 sites in 28 countries

Germany17 sites
  • Research Site

    Augsburg

  • Research Site

    Berlin

  • Research Site

    Cologne

  • Research Site

    Essen

  • Research Site

    Freiburg im Breisgau

  • Research Site

    Gauting

  • Research Site

    Göttingen

  • Research Site

    Großhansdorf

  • Research Site

    Halle-Dölau

  • Research Site

    Hamburg

  • Research Site

    Heidelberg

  • Research Site

    Löwenstein

  • Research Site

    Magdeburg

  • Research Site

    Mainz

  • Research Site

    München

  • Research Site

    Stralsund

  • Research Site

    Wuppertal

Other trials in Germany

Spain11 sites
  • Research Site

    Barakaldo (Bilbao)

  • Research Site

    Barcelona

  • Research Site

    Donostia / San Sebastian

  • Research Site

    Elche Alicante

  • Research Site

    Granollers

  • Research Site

    Madrid

  • Research Site

    Pamplona

  • Research Site

    Pontevedra

  • Research Site

    Santander

  • Research Site

    Terrassa

  • Research Site

    Valencia

Other trials in Spain

France9 sites
  • Research Site

    Brest

  • Research Site

    Caen

  • Research Site

    Grenoble

  • Research Site

    Marseille

  • Research Site

    Paris

  • Research Site

    Poitiers

  • Research Site

    Rennes

  • Research Site

    Rouen

  • Research Site

    Strasbourg

Other trials in France

United Kingdom9 sites
  • Research Site

    Aberdeen

  • Research Site

    Bristol

  • Research Site

    Edinburgh

  • Research Site

    Leicester

  • Research Site

    London

  • Research Site

    Newcastle upon Tyne

  • Research Site

    Poole

  • Research Site

    Sutton

  • Research Site

    Wolverhampton

Other trials in United Kingdom

Ukraine8 sites
  • Research Site

    Dnipropetrovsk

  • Research Site

    Kharkiv

  • Research Site

    Kyiv

  • Research Site

    Lviv

  • Research Site

    Poltava

  • Research Site

    Sumy

  • Research Site

    Ternopil

  • Research Site

    Uzhhorod

Other trials in Ukraine

Hungary6 sites
  • Research Site

    Budapest

  • Research Site

    Nyiregyháza

  • Research Site

    Székesfehérvár

  • Research Site

    Szombathely

  • Research Site

    Törökbálint

  • Research Site

    Zalegerzeg-Pózva

Other trials in Hungary

Italy6 sites
  • Research Site

    Bologna

  • Research Site

    Carpi

  • Research Site

    Milan

  • Research Site

    Rome

  • Research Site

    Rozzano-Milano

  • Research Site

    Treviglio

Other trials in Italy

Poland6 sites
  • Research Site

    Bydgoszcz

  • Research Site

    Olsztyn

  • Research Site

    Otwock

  • Research Site

    Posnan

  • Research Site

    Warsaw

  • Research Site

    Wroclaw

Other trials in Poland

Australia5 sites
  • Research Site

    Adelaide

  • Research Site

    Melbourne

  • Research Site

    Randwick

  • Research Site

    Sydney

  • Research Site

    Wodonga

Other trials in Australia

Bulgaria4 sites
  • Research Site

    Pleven

  • Research Site

    Sofia

  • Research Site

    Stara Zagora

  • Research Site

    Veliko Tarnovo

Other trials in Bulgaria

Czechia4 sites
  • Research Site

    Brno

  • Research Site

    Ostrava

  • Research Site

    Pilsen

  • Research Site

    Prague

Other trials in Czechia

Slovakia4 sites
  • Research Site

    Banská Bystrica

  • Research Site

    Bratislava

  • Research Site

    Nitra-Zobor

  • Research Site

    Poprad

Other trials in Slovakia

Belgium3 sites
  • Research Site

    Brussels

  • Research Site

    Charleroi

  • Research Site

    Liège

Other trials in Belgium

Netherlands3 sites
  • Research Site

    Amsterdam

  • Research Site

    Nieuwegeln

  • Research Site

    Zwolle

Other trials in Netherlands

Switzerland3 sites
  • Research Site

    Bern

  • Research Site

    Thun

  • Research Site

    Zurich

Other trials in Switzerland

Argentina2 sites
  • Research Site

    Buenos Aires

  • Research Site

    Córdoba

Other trials in Argentina

Brazil2 sites
  • Research Site

    Porto Alegre

  • Research Site

    São Paulo

Other trials in Brazil

Chile2 sites
  • Research Site

    Antofagasta

  • Research Site

    Santiago

Other trials in Chile

Mexico2 sites
  • Research Site

    Mexico City

  • Research Site

    Monterrey

Other trials in Mexico

Russia2 sites
  • Research Site

    Moscow

  • Research Site

    Saint Petersburg

Other trials in Russia

Sweden2 sites
  • Research Site

    Stockholm

  • Research Site

    Uppsala

Other trials in Sweden

Taiwan2 sites
  • Research Site

    Taipei, Tao Yuan County

  • Research Site

    Taipei

Other trials in Taiwan

Austria1 site
  • Research Site

    Vienna

Other trials in Austria

Hong Kong1 site
  • Research Site

    Honh Kong

Other trials in Hong Kong

Ireland1 site
  • Research Site

    Dublin

Other trials in Ireland

Singapore1 site
  • Research Site

    Singapore

Other trials in Singapore

South Korea1 site
  • Research Site

    Seoul

Other trials in South Korea

Turkey (Türkiye)1 site
  • Research Site

    Ankara

Other trials in Turkey (Türkiye)

About this study

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.

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.

Being tested
cetuximab + cisplatin + vinorelbine, cisplatin + vinorelbine
Keywords
Cetuximab, Non small cell lung cancer, Lung cancer, Cisplatin/vinorelbine, Monoclonal antibody, Erbitux
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cetuximab + cisplatin + vinorelbineDrug

    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 + vinorelbineDrug

    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.

Study groups in NCT00148798
Study groupRoleWhat they receive
Cetuximab plus chemotherapyExperimentalcetuximab + cisplatin + vinorelbine
Receives: Drug: cetuximab + cisplatin + vinorelbine
Chemotherapy aloneActive comparatorcisplatin + vinorelbine alone
Receives: Drug: cisplatin + vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)
  1. 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.

    Measured: 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

  2. 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).

    Measured: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007

  3. 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).

    Measured: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007

  4. 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.

    Measured: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007

  5. 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.

    Measured: at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007

  6. 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.

    Measured: Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.

  7. Safety - Number of Patients Experiencing Any Adverse Event

    Please refer to Adverse Events section for further details

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2005 (estimated)
  2. Study startOct 2004
  3. Primary completionJul 2007
  4. Study completionMay 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,861 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00148798
Sponsor's protocol ID
EMR 62202-046
Acronym
FLEX
Status last verified
Jun 2014
First submitted
7 Sep 2005
Last updated
25 Jun 2014
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19410716
  • 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.

    PubMed 22498112
  • 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.

    PubMed 22056021
  • 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.

    PubMed 21782507
  • 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.

    PubMed 21169060

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cetuximab + cisplatin + vinorelbine and cisplatin + vinorelbine in people with Non Small Cell Lung Cancer (NSCLC), run by Merck KGaA, Darmstadt, Germany at 118 sites in 28 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 118 sites in Germany, Spain, France, United Kingdom, Ukraine and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival Time (OS) (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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00148798, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2014.

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