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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00148798
First received: September 7, 2005
Last updated: December 20, 2012
Last verified: December 2012
Results First Received: August 24, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non Small Cell Lung Cancer (NSCLC)
Interventions: Drug: cetuximab + cisplatin + vinorelbine
Drug: cisplatin + vinorelbine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First/last subject (informed consent): October 2004/January 2006. Clinical data cut-off: 18 July 2007. Last subject completed 16 May 2012. Subjects randomized at 155 centers; Asia/Australia: 21; Europe: 120; South America: 14.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled: 1,861 after consent to epidermal growth factor receptor (EGFR) assessment; 603 excluded (mainly non-fulfillment of inclusion or exclusion criteria). 1,258 screened for eligibility after consent for study procedures; 143 excluded (mainly non-fulfillment of inclusion or exclusion criteria). 1,125 subjects randomized.

Reporting Groups
  Description
Cetuximab Plus Chemotherapy

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.

Safety population: includes all treated subjects.

Chemotherapy Alone

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.

Safety population: includes all treated subjects.


Participant Flow:   Overall Study
    Cetuximab Plus Chemotherapy     Chemotherapy Alone  
STARTED     557 [1]   568 [2]
COMPLETED     557     568  
NOT COMPLETED     0     0  
[1] Intent To Treat (ITT) Population
[2] ITT Population



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cetuximab Plus Chemotherapy

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.

Safety population: includes all treated subjects.

Chemotherapy Alone

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.

Safety population: includes all treated subjects.

Total Total of all reporting groups

Baseline Measures
    Cetuximab Plus Chemotherapy     Chemotherapy Alone     Total  
Number of Participants  
[units: participants]
  557     568     1125  
Age  
[units: years]
Median ( Full Range )
  59  
  ( 18 to 78 )  
  60  
  ( 20 to 83 )  
  59  
  ( 18 to 83 )  
Age, Customized  
[units: participants]
     
<18 years     0     0     0  
Between 18 and 65 years     385     389     774  
>=65 years     172     179     351  
Gender  
[units: participants]
     
Female     172     163     335  
Male     385     405     790  
Region of Enrollment  
[units: participants]
     
Australia     20     23     43  
Hong Kong     2     2     4  
Singapore     5     5     10  
Korea, Republic of     28     26     54  
Taiwan     21     22     43  
Austria     9     7     16  
Belgium     3     10     13  
Bulgaria     12     12     24  
Czech Republic     12     17     29  
France     25     25     50  
Germany     91     88     179  
Hungary     21     23     44  
Ireland     3     4     7  
Netherlands     10     10     20  
Poland     59     50     109  
Portugal     3     0     3  
Russian Federation     23     16     39  
Slovakia     8     12     20  
Spain     16     13     29  
Sweden     6     3     9  
Switzerland     10     6     16  
Turkey     1     2     3  
United Kingdom     23     21     44  
Ukraine     56     71     127  
Chile     10     16     26  
Italy     18     23     41  
Argentina     5     2     7  
Mexico     9     8     17  
Brazil     48     51     99  



  Outcome Measures
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1.  Primary:   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 ]

2.  Secondary:   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 ]

3.  Secondary:   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 ]

4.  Secondary:   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 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Disease Control Rate
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT

Reporting Groups
  Description
Cetuximab Plus Chemotherapy

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.

Safety population: includes all treated subjects.

Chemotherapy Alone

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.

Safety population: includes all treated subjects.


Measured Values
    Cetuximab Plus Chemotherapy     Chemotherapy Alone  
Number of Participants Analyzed  
[units: participants]
  557     568  
Disease Control Rate  
[units: percentage¬†of¬†participants]
Number ( 95% Confidence Interval )
  72.5  
  ( 68.6 to 76.2 )  
  71.5  
  ( 67.6 to 75.2 )  


Statistical Analysis 1 for Disease Control Rate
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.6801
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The disease control rate was compared in the Cochran-Mantel-Haenszel test (two-sided with α=5%).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



5.  Secondary:   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 ]

6.  Secondary:   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 ]

7.  Secondary:   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. ]

8.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Merck KGaA Communication Center
Organization: Merck KGaA
phone: +49-6151-72-5200
e-mail: service@merck.de


Publications of Results:
Publications automatically indexed to this study:


Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00148798     History of Changes
Other Study ID Numbers: EMR 62202-046
Study First Received: September 7, 2005
Results First Received: August 24, 2011
Last Updated: December 20, 2012
Health Authority: Austria: Federal Ministry for Health and Women