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

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ClinicalTrials.gov Identifier: NCT00148798
Recruitment Status : Completed
First Posted : September 8, 2005
Results First Posted : October 4, 2011
Last Update Posted : June 25, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Non Small Cell Lung Cancer (NSCLC)
Interventions: Drug: cetuximab + cisplatin + vinorelbine
Drug: cisplatin + vinorelbine

  Participant Flow

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

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 
Overall Participants Analyzed 
[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

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 ]
  Show Outcome Measure 1

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 ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Progression-free Survival Time
Measure Description

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 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  

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 
Participants Analyzed 
[Units: Participants]
 		 557   568 
Progression-free Survival Time 
[Units: Months]
Median (95% Confidence Interval) 		 4.8 
 (4.2 to 5.3)  		 4.8 
 (4.4 to 5.4) 


Statistical Analysis 1 for Progression-free Survival Time
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Stratified Log Rank
P Value [4] 0.3869
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  To test equality of progression free survival time between treatment groups, applying the two-sided stratified log-rank test (α=5%).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.



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 ]
  Show Outcome Measure 3

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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. ]
  Show Outcome Measure 7

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 ]
  Show Outcome Measure 8


  Serious Adverse Events


  Other Adverse Events


  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.


  More Information