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

June 13, 2014 updated by: Merck KGaA, Darmstadt, Germany

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1861

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Research Site
      • Cordoba, Argentina
        • Research Site
  • Australia
      • Adelaide, Australia
        • Research Site
      • Melbourne, Australia
        • Research Site
      • Randwick, Australia
        • Research Site
      • Sydney, Australia
        • Research Site
      • Wodonga, Australia
        • Research Site
  • Austria
      • Wien, Austria
        • Research Site
  • Belgium
      • Bruxelles, Belgium
        • Research Site
      • Charleroi, Belgium
        • Research Site
      • Liège, Belgium
        • Research Site
  • Brazil
      • Porto Alegre, Brazil
        • Research Site
      • Sao Paulo, Brazil
        • Research Site
  • Bulgaria
      • Pleven, Bulgaria
        • Research Site
      • Sofia, Bulgaria
        • Research Site
      • Stara Zagora, Bulgaria
        • Research Site
      • Veliko Tarnovo, Bulgaria
        • Research Site
  • Chile
      • Antofagasta, Chile
        • Research Site
      • Santiago de Chile, Chile
        • Research Site
  • Czech Republic
      • Brno, Czech Republic
        • Research Site
      • Ostrava, Czech Republic
        • Research Site
      • Pilsen, Czech Republic
        • Research Site
      • Praha, Czech Republic
        • Research Site
  • France
      • Brest, France
        • Research Site
      • Caen, France
        • Research Site
      • Grenoble, France
        • Research Site
      • Marseille, France
        • Research Site
      • Paris, France
        • Research Site
      • Poitiers, France
        • Research Site
      • Rennes, France
        • Research Site
      • Rouen, France
        • Research Site
      • Strasbourg, France
        • Research Site
  • Germany
      • Augsburg, Germany
        • Research Site
      • Berlin, Germany
        • Research Site
      • Essen, Germany
        • Research Site
      • Freiburg, Germany
        • Research Site
      • Gauting, Germany
        • Research Site
      • Großhansdorf, Germany
        • Research Site
      • Göttingen, Germany
        • Research Site
      • Halle-Dölau, Germany
        • Research Site
      • Hamburg, Germany
        • Research Site
      • Heidelberg, Germany
        • Research Site
      • Köln, Germany
        • Research Site
      • Löwenstein, Germany
        • Research Site
      • Magdeburg, Germany
        • Research Site
      • Mainz, Germany
        • Research Site
      • München, Germany
        • Research Site
      • Stralsund, Germany
        • Research Site
      • Wuppertal, Germany
        • Research Site
  • Hong Kong
      • Honh Kong, Hong Kong
        • Research Site
  • Hungary
      • Budapest, Hungary
        • Research Site
      • Nyiregyháza, Hungary
        • Research Site
      • Szombathely, Hungary
        • Research Site
      • Székesfehérvár, Hungary
        • Research Site
      • Torokbalint, Hungary
        • Research Site
      • Zalegerzeg-Pózva, Hungary
        • Research Site
  • Ireland
      • Dublin, Ireland
        • Research Site
  • Italy
      • Bologna, Italy
        • Research Site
      • Carpi, Italy
        • Research Site
      • Milano, Italy
        • Research Site
      • Rome, Italy
        • Research Site
      • Rozzano-Milano, Italy
        • Research Site
      • Treviglio, Italy
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Research Site
  • Mexico
      • Mexico-City, Mexico
        • Research Site
      • Monterrey, Mexico
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands
        • Research Site
      • Nieuwegeln, Netherlands
        • Research Site
      • Zwolle, Netherlands
        • Research Site
  • Poland
      • Bydgoszcz, Poland
        • Research Site
      • Olsztyn, Poland
        • Research Site
      • Otwock, Poland
        • Research Site
      • Posnan, Poland
        • Research Site
      • Warszawa, Poland
        • Research Site
      • Wroclaw, Poland
        • Research Site
  • Russian Federation
      • Moscow, Russian Federation
        • Research Site
      • St. Petersburg, Russian Federation
        • Research Site
  • Singapore
      • Singapore, Singapore
        • Research Site
  • Slovakia
      • Banska Bystrica, Slovakia
        • Research Site
      • Bratislava, Slovakia
        • Research Site
      • Nitra-Zobor, Slovakia
        • Research Site
      • Poprad, Slovakia
        • Research Site
  • Spain
      • Barakaldo (Bilbao), Spain
        • Research Site
      • Barcelona, Spain
        • Research Site
      • Elche Alicante, Spain
        • Research Site
      • Granollers, Spain
        • Research Site
      • Madrid, Spain
        • Research Site
      • Pamplona, Spain
        • Research Site
      • Pontevedra, Spain
        • Research Site
      • San Sebastian, Spain
        • Research Site
      • Santander, Spain
        • Research Site
      • Terrassa, Spain
        • Research Site
      • Valencia, Spain
        • Research Site
  • Sweden
      • Stockholm, Sweden
        • Research Site
      • Uppsala, Sweden
        • Research Site
  • Switzerland
      • Bern, Switzerland
        • Research Site
      • Thun, Switzerland
        • Research Site
      • Zürich, Switzerland
        • Research Site
  • Taiwan
      • Taipei, Taiwan
        • Research Site
    • Tao Yuan County
      • Taipei, Tao Yuan County, Taiwan
        • Research Site
  • Turkey
      • Ankara, Turkey
        • Research Site
  • Ukraine
      • Dnipropetrovsk, Ukraine
        • Research Site
      • Kharkiv, Ukraine
        • Research Site
      • Kyiv, Ukraine
        • Research Site
      • Lviv, Ukraine
        • Research Site
      • Poltava, Ukraine
        • Research Site
      • Sumy, Ukraine
        • Research Site
      • Ternopol, Ukraine
        • Research Site
      • Uzhgorod, Ukraine
        • Research Site
  • United Kingdom
      • Aberdeen, United Kingdom
        • Research Site
      • Bristol, United Kingdom
        • Research Site
      • Edinburgh, United Kingdom
        • Research Site
      • Leicester, United Kingdom
        • Research Site
      • London, United Kingdom
        • Research Site
      • Newcastle upon Tyne, United Kingdom
        • Research Site
      • Poole, United Kingdom
        • Research Site
      • Sutton, United Kingdom
        • Research Site
      • Wolverhampton, United Kingdom
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cetuximab plus chemotherapy
cetuximab + cisplatin + vinorelbine
Drug: 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.
Active Comparator: Chemotherapy alone
cisplatin + vinorelbine alone
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival Time
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

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 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
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
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).
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
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
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).
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
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
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.
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
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
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.
at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007
A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations
Time Frame: Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
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.
Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.
Safety - Number of Patients Experiencing Any Adverse Event
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
Please refer to Adverse Events section for further details
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck KGaA, Darmstadt, Germany

Investigators

  • Principal Investigator: Robert Pirker, Professor, Universitätsklinik für Innere Medizin I, Wien

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 7, 2005

First Posted (Estimate)

September 8, 2005

Study Record Updates

Last Update Posted (Estimate)

June 25, 2014

Last Update Submitted That Met QC Criteria

June 13, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMR 62202-046

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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