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

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148798
• Other study ID #: EMR 62202-046
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: June 13, 2014
• Start date: October 2004
• Est. completion date: May 2012

Study information

• Verified date: June 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1861
• Est. completion date: May 2012
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer (NSCLC)

Intervention

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.
• 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.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Cordoba
Australia	Research Site	Adelaide
Australia	Research Site	Melbourne
Australia	Research Site	Randwick
Australia	Research Site	Sydney
Australia	Research Site	Wodonga
Austria	Research Site	Wien
Belgium	Research Site	Bruxelles
Belgium	Research Site	Charleroi
Belgium	Research Site	Liège
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Paulo
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Veliko Tarnovo
Chile	Research Site	Antofagasta
Chile	Research Site	Santiago de Chile
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Ostrava
Czech Republic	Research Site	Pilsen
Czech Republic	Research Site	Praha
France	Research Site	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
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Freiburg
Germany	Research Site	Gauting
Germany	Research Site	Göttingen
Germany	Research Site	Großhansdorf
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
Hong Kong	Research Site	Honh Kong
Hungary	Research Site	Budapest
Hungary	Research Site	Nyiregyháza
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Szombathely
Hungary	Research Site	Torokbalint
Hungary	Research Site	Zalegerzeg-Pózva
Ireland	Research Site	Dublin
Italy	Research Site	Bologna
Italy	Research Site	Carpi
Italy	Research Site	Milano
Italy	Research Site	Rome
Italy	Research Site	Rozzano-Milano
Italy	Research Site	Treviglio
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Mexico-City
Mexico	Research Site	Monterrey
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Nieuwegeln
Netherlands	Research Site	Zwolle
Poland	Research Site	Bydgoszcz
Poland	Research Site	Olsztyn
Poland	Research Site	Otwock
Poland	Research Site	Posnan
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	St. Petersburg
Singapore	Research Site	Singapore
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Nitra-Zobor
Slovakia	Research Site	Poprad
Spain	Research Site	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
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Switzerland	Research Site	Bern
Switzerland	Research Site	Thun
Switzerland	Research Site	Zürich
Taiwan	Research Site	Taipei	Tao Yuan County
Taiwan	Research Site	Taipei
Turkey	Research Site	Ankara
Ukraine	Research Site	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
United Kingdom	Research Site	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

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Chile,  Czech Republic,  France,  Germany,  Hong Kong,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Singapore,  Slovakia,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

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 pati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	No
Secondary	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.	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	No
Secondary	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).	Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007	No
Secondary	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).	Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007	No
Secondary	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.	at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007	No
Secondary	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.	at baseline, at cycle 3, at month 6, reported between day of first patient randomised, Oct 2004, until cut-off date 18 Jul 2007	No
Secondary	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.	Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration.	No
Secondary	Safety - Number of Patients Experiencing Any Adverse Event	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	Yes