Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX) (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: June 13, 2014

Last verified: June 2014

History of Changes

Results First Received: August 24, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; 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.

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.
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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

Description

Cetuximab Plus Chemotherapy

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

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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 ]

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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 ]

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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.

Description

Cetuximab Plus Chemotherapy

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 ]

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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 ]

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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 ]

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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 ]

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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. ]

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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 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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
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