Study of Cisplatin/Vinorelbine +/- Cetuximab as First-line Treatment of Advanced Non Small Cell Lung Cancer (FLEX)
Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT00148798
Collaborator
(none)
1,861
118
2
91
15.8
0.2
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1861 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Study Start Date
:
Oct 1, 2004
Actual Primary Completion Date
:
Jul 1, 2007
Actual Study Completion Date
:
May 1, 2012
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival Time (OS) [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.
Secondary Outcome Measures
- Progression-free Survival Time [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.
- Best Overall Response Rate [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).
- Disease Control Rate [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).
- Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status [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.
- Quality of Life Assessment (EORTC QLQ-C30) Social 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]
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.
- A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations [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.
- Safety - Number of Patients Experiencing Any Adverse Event [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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Buenos Aires | Argentina | ||
| 2 | Research Site | Cordoba | Argentina | ||
| 3 | Research Site | Adelaide | Australia | ||
| 4 | Research Site | Melbourne | Australia | ||
| 5 | Research Site | Randwick | Australia | ||
| 6 | Research Site | Sydney | Australia | ||
| 7 | Research Site | Wodonga | Australia | ||
| 8 | Research Site | Wien | Austria | ||
| 9 | Research Site | Bruxelles | Belgium | ||
| 10 | Research Site | Charleroi | Belgium | ||
| 11 | Research Site | Liège | Belgium | ||
| 12 | Research Site | Porto Alegre | Brazil | ||
| 13 | Research Site | Sao Paulo | Brazil | ||
| 14 | Research Site | Pleven | Bulgaria | ||
| 15 | Research Site | Sofia | Bulgaria | ||
| 16 | Research Site | Stara Zagora | Bulgaria | ||
| 17 | Research Site | Veliko Tarnovo | Bulgaria | ||
| 18 | Research Site | Antofagasta | Chile | ||
| 19 | Research Site | Santiago de Chile | Chile | ||
| 20 | Research Site | Brno | Czech Republic | ||
| 21 | Research Site | Ostrava | Czech Republic | ||
| 22 | Research Site | Pilsen | Czech Republic | ||
| 23 | Research Site | Praha | Czech Republic | ||
| 24 | Research Site | Brest | France | ||
| 25 | Research Site | Caen | France | ||
| 26 | Research Site | Grenoble | France | ||
| 27 | Research Site | Marseille | France | ||
| 28 | Research Site | Paris | France | ||
| 29 | Research Site | Poitiers | France | ||
| 30 | Research Site | Rennes | France | ||
| 31 | Research Site | Rouen | France | ||
| 32 | Research Site | Strasbourg | France | ||
| 33 | Research Site | Augsburg | Germany | ||
| 34 | Research Site | Berlin | Germany | ||
| 35 | Research Site | Essen | Germany | ||
| 36 | Research Site | Freiburg | Germany | ||
| 37 | Research Site | Gauting | Germany | ||
| 38 | Research Site | Großhansdorf | Germany | ||
| 39 | Research Site | Göttingen | Germany | ||
| 40 | Research Site | Halle-Dölau | Germany | ||
| 41 | Research Site | Hamburg | Germany | ||
| 42 | Research Site | Heidelberg | Germany | ||
| 43 | Research Site | Köln | Germany | ||
| 44 | Research Site | Löwenstein | Germany | ||
| 45 | Research Site | Magdeburg | Germany | ||
| 46 | Research Site | Mainz | Germany | ||
| 47 | Research Site | München | Germany | ||
| 48 | Research Site | Stralsund | Germany | ||
| 49 | Research Site | Wuppertal | Germany | ||
| 50 | Research Site | Honh Kong | Hong Kong | ||
| 51 | Research Site | Budapest | Hungary | ||
| 52 | Research Site | Nyiregyháza | Hungary | ||
| 53 | Research Site | Szombathely | Hungary | ||
| 54 | Research Site | Székesfehérvár | Hungary | ||
| 55 | Research Site | Torokbalint | Hungary | ||
| 56 | Research Site | Zalegerzeg-Pózva | Hungary | ||
| 57 | Research Site | Dublin | Ireland | ||
| 58 | Research Site | Bologna | Italy | ||
| 59 | Research Site | Carpi | Italy | ||
| 60 | Research Site | Milano | Italy | ||
| 61 | Research Site | Rome | Italy | ||
| 62 | Research Site | Rozzano-Milano | Italy | ||
| 63 | Research Site | Treviglio | Italy | ||
| 64 | Research Site | Seoul | Korea, Republic of | ||
| 65 | Research Site | Mexico-City | Mexico | ||
| 66 | Research Site | Monterrey | Mexico | ||
| 67 | Research Site | Amsterdam | Netherlands | ||
| 68 | Research Site | Nieuwegeln | Netherlands | ||
| 69 | Research Site | Zwolle | Netherlands | ||
| 70 | Research Site | Bydgoszcz | Poland | ||
| 71 | Research Site | Olsztyn | Poland | ||
| 72 | Research Site | Otwock | Poland | ||
| 73 | Research Site | Posnan | Poland | ||
| 74 | Research Site | Warszawa | Poland | ||
| 75 | Research Site | Wroclaw | Poland | ||
| 76 | Research Site | Moscow | Russian Federation | ||
| 77 | Research Site | St. Petersburg | Russian Federation | ||
| 78 | Research Site | Singapore | Singapore | ||
| 79 | Research Site | Banska Bystrica | Slovakia | ||
| 80 | Research Site | Bratislava | Slovakia | ||
| 81 | Research Site | Nitra-Zobor | Slovakia | ||
| 82 | Research Site | Poprad | Slovakia | ||
| 83 | Research Site | Barakaldo (Bilbao) | Spain | ||
| 84 | Research Site | Barcelona | Spain | ||
| 85 | Research Site | Elche Alicante | Spain | ||
| 86 | Research Site | Granollers | Spain | ||
| 87 | Research Site | Madrid | Spain | ||
| 88 | Research Site | Pamplona | Spain | ||
| 89 | Research Site | Pontevedra | Spain | ||
| 90 | Research Site | San Sebastian | Spain | ||
| 91 | Research Site | Santander | Spain | ||
| 92 | Research Site | Terrassa | Spain | ||
| 93 | Research Site | Valencia | Spain | ||
| 94 | Research Site | Stockholm | Sweden | ||
| 95 | Research Site | Uppsala | Sweden | ||
| 96 | Research Site | Bern | Switzerland | ||
| 97 | Research Site | Thun | Switzerland | ||
| 98 | Research Site | Zürich | Switzerland | ||
| 99 | Research Site | Taipei | Tao Yuan County | Taiwan | |
| 100 | Research Site | Taipei | Taiwan | ||
| 101 | Research Site | Ankara | Turkey | ||
| 102 | Research Site | Dnipropetrovsk | Ukraine | ||
| 103 | Research Site | Kharkiv | Ukraine | ||
| 104 | Research Site | Kyiv | Ukraine | ||
| 105 | Research Site | Lviv | Ukraine | ||
| 106 | Research Site | Poltava | Ukraine | ||
| 107 | Research Site | Sumy | Ukraine | ||
| 108 | Research Site | Ternopol | Ukraine | ||
| 109 | Research Site | Uzhgorod | Ukraine | ||
| 110 | Research Site | Aberdeen | United Kingdom | ||
| 111 | Research Site | Bristol | United Kingdom | ||
| 112 | Research Site | Edinburgh | United Kingdom | ||
| 113 | Research Site | Leicester | United Kingdom | ||
| 114 | Research Site | London | United Kingdom | ||
| 115 | Research Site | Newcastle upon Tyne | United Kingdom | ||
| 116 | Research Site | Poole | United Kingdom | ||
| 117 | Research Site | Sutton | United Kingdom | ||
| 118 | Research Site | Wolverhampton | United Kingdom |
Sponsors and Collaborators
- Merck KGaA, Darmstadt, Germany
Investigators
- Principal Investigator: Robert Pirker, Professor, Universitätsklinik für Innere Medizin I, Wien
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT00148798
Other Study ID Numbers:
- EMR 62202-046
First Posted:
Sep 8, 2005
Last Update Posted:
Jun 25, 2014
Last Verified:
Jun 1, 2014
Keywords provided by Merck KGaA, Darmstadt, Germany
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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 Detail | 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. |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 557 | 568 |
| COMPLETED | 557 | 568 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 of all reporting groups |
| Overall Participants | 557 | 568 | 1125 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
59
|
60
|
59
|
| Age, Customized (participants) [Number] | |||
| <18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
385
69.1%
|
389
68.5%
|
774
68.8%
|
| >=65 years |
172
30.9%
|
179
31.5%
|
351
31.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
172
30.9%
|
163
28.7%
|
335
29.8%
|
| Male |
385
69.1%
|
405
71.3%
|
790
70.2%
|
| Region of Enrollment (participants) [Number] | |||
| Australia |
20
3.6%
|
23
4%
|
43
3.8%
|
| Hong Kong |
2
0.4%
|
2
0.4%
|
4
0.4%
|
| Singapore |
5
0.9%
|
5
0.9%
|
10
0.9%
|
| Korea, Republic of |
28
5%
|
26
4.6%
|
54
4.8%
|
| Taiwan |
21
3.8%
|
22
3.9%
|
43
3.8%
|
| Austria |
9
1.6%
|
7
1.2%
|
16
1.4%
|
| Belgium |
3
0.5%
|
10
1.8%
|
13
1.2%
|
| Bulgaria |
12
2.2%
|
12
2.1%
|
24
2.1%
|
| Czech Republic |
12
2.2%
|
17
3%
|
29
2.6%
|
| France |
25
4.5%
|
25
4.4%
|
50
4.4%
|
| Germany |
91
16.3%
|
88
15.5%
|
179
15.9%
|
| Hungary |
21
3.8%
|
23
4%
|
44
3.9%
|
| Ireland |
3
0.5%
|
4
0.7%
|
7
0.6%
|
| Netherlands |
10
1.8%
|
10
1.8%
|
20
1.8%
|
| Poland |
59
10.6%
|
50
8.8%
|
109
9.7%
|
| Portugal |
3
0.5%
|
0
0%
|
3
0.3%
|
| Russian Federation |
23
4.1%
|
16
2.8%
|
39
3.5%
|
| Slovakia |
8
1.4%
|
12
2.1%
|
20
1.8%
|
| Spain |
16
2.9%
|
13
2.3%
|
29
2.6%
|
| Sweden |
6
1.1%
|
3
0.5%
|
9
0.8%
|
| Switzerland |
10
1.8%
|
6
1.1%
|
16
1.4%
|
| Turkey |
1
0.2%
|
2
0.4%
|
3
0.3%
|
| United Kingdom |
23
4.1%
|
21
3.7%
|
44
3.9%
|
| Ukraine |
56
10.1%
|
71
12.5%
|
127
11.3%
|
| Chile |
10
1.8%
|
16
2.8%
|
26
2.3%
|
| Italy |
18
3.2%
|
23
4%
|
41
3.6%
|
| Argentina |
5
0.9%
|
2
0.4%
|
7
0.6%
|
| Mexico |
9
1.6%
|
8
1.4%
|
17
1.5%
|
| Brazil |
48
8.6%
|
51
9%
|
99
8.8%
|
Outcome Measures
| Title | Overall Survival Time (OS) |
|---|---|
| Description | 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 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 557 | 568 |
| Median (95% Confidence Interval) [months] |
11.3
|
10.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cetuximab Plus Chemotherapy, Chemotherapy Alone |
|---|---|---|
| Comments | Primary efficacy analysis: To test equality of OS time between treatment groups, applying the two-sided stratified log-rank test (Stage IIIb vs IV, ECOG 0/1 vs 2) (α=5%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0441 |
| Comments | ||
| Method | Stratified Log Rank | |
| Comments | ||
| Title | Progression-free Survival Time |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 557 | 568 |
| Median (95% Confidence Interval) [months] |
4.8
|
4.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cetuximab Plus Chemotherapy, Chemotherapy Alone |
|---|---|---|
| Comments | To test equality of progression free survival time between treatment groups, applying the two-sided stratified log-rank test (α=5%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3869 |
| Comments | ||
| Method | Stratified Log Rank | |
| Comments | ||
| Title | Best Overall Response Rate |
|---|---|
| Description | 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). |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 557 | 568 |
| Number (95% Confidence Interval) [percentage of participants] |
36.4
6.5%
|
29.2
5.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cetuximab Plus Chemotherapy, Chemotherapy Alone |
|---|---|---|
| Comments | The best overall response rate was compared in the Cochran-Mantel-Haenszel test (two-sided with α=5%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0101 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Disease Control Rate |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 557 | 568 |
| Number (95% Confidence Interval) [percentage of participants] |
72.5
13%
|
71.5
12.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cetuximab Plus Chemotherapy, Chemotherapy Alone |
|---|---|---|
| Comments | The disease control rate was compared in the Cochran-Mantel-Haenszel test (two-sided with α=5%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6801 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 670 subjects completed (348 in the cetuximab + chemotherapy arm and 322 in the chemotherapy alone arm) at least 1 evaluable QLQ-C30 questionnaire and were included in the Evaluable population. Numbers at each timepoint were (Cetuximab + chemotherapy/Chemotherapy alone, respectively): baseline 278/274; cycle 3 184/153; 6 month 102/96 |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 348 | 322 |
| At baseline |
45.72
(2.164)
|
46.36
(2.138)
|
| At cycle 3 |
48.33
(2.325)
|
51.55
(2.464)
|
| At month 6 |
54.71
(2.729)
|
52.92
(2.787)
|
| Title | Quality of Life Assessment (EORTC QLQ-C30) Social Functioning |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 670 subjects completed (348 in the cetuximab + chemotherapy arm and 322 in the chemotherapy alone arm) at least 1 evaluable QLQ-C30 questionnaire and were included in the Evaluable population. Numbers at each timepoint were (Cetuximab + chemotherapy/Chemotherapy alone, respectively): baseline 280/275; cycle 3 185/153; 6 month 101/97 |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 348 | 322 |
| At baseline |
66.17
(2.836)
|
64.73
(2.825)
|
| At cycle 3 |
58.05
(2.995)
|
67.13
(3.138)
|
| At month 6 |
67.36
(3.449)
|
66.47
(3.515)
|
| Title | A Population Pharmacokinetic (PK) Analysis for Cetuximab in Non-Small Cell Lung Cancer (NSCLC) - Serum Cetuximab Concentrations |
|---|---|
| Description | 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. |
| Time Frame | Week 1, Day 1: baseline and end of infusion; Week 7, Day 43: within 12 h after cetuximab administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cetuximab Concentration at End of Infusion Week 1 | Cetuximab Concentration Before Infusion Week 7 |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 454 | 298 |
| Mean (Standard Deviation) [ug/mL] |
223.1
(64.6)
|
51.5
(33.1)
|
| Title | Safety - Number of Patients Experiencing Any Adverse Event |
|---|---|
| Description | Please refer to Adverse Events section for further details |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 548 | 562 |
| Number [participants] |
545
97.8%
|
549
96.7%
|
Adverse Events
| Time Frame | Time from first dose up to 30 days after the last dose of study treatment. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent adverse events were defined as those with onset occurring at or after the first dosing day of study medication and up to 30 days after the last administration of any study drug or the clinical cut-off date. | |||
| Arm/Group Title | Cetuximab Plus Chemotherapy | Chemotherapy Alone | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Cetuximab Plus Chemotherapy | Chemotherapy Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Cetuximab Plus Chemotherapy | Chemotherapy Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 325/548 (59.3%) | 244/562 (43.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 11/548 (2%) | 12/562 (2.1%) | ||
| Febrile bone marrow aplasia | 4/548 (0.7%) | 0/562 (0%) | ||
| Febrile neutropenia | 96/548 (17.5%) | 67/562 (11.9%) | ||
| Granulocytopenia | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Leukopenia | 15/548 (2.7%) | 8/562 (1.4%) | ||
| Neutropenia | 47/548 (8.6%) | 33/562 (5.9%) | ||
| Pancytopenia | 2/548 (0.4%) | 0/562 (0%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 4/548 (0.7%) | 0/562 (0%) | ||
| Angina pectoris | 0/548 (0%) | 1/562 (0.2%) | ||
| Arrhythmia supraventricular | 1/548 (0.2%) | 0/562 (0%) | ||
| Atrial fibrillation | 0/548 (0%) | 4/562 (0.7%) | ||
| Cardiac arrest | 0/548 (0%) | 2/562 (0.4%) | ||
| Cardiac failure | 1/548 (0.2%) | 2/562 (0.4%) | ||
| Cardiac failure acute | 2/548 (0.4%) | 0/562 (0%) | ||
| Cardiac tamponade | 1/548 (0.2%) | 0/562 (0%) | ||
| Cardio-respiratory arrest | 1/548 (0.2%) | 0/562 (0%) | ||
| Cardiogenic shock | 1/548 (0.2%) | 0/562 (0%) | ||
| Cardiopulmonary failure | 3/548 (0.5%) | 3/562 (0.5%) | ||
| Left ventricular failure | 2/548 (0.4%) | 0/562 (0%) | ||
| Microvascular angina | 1/548 (0.2%) | 0/562 (0%) | ||
| Myocardial infarction | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Myocardial ischaemia | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Palpitations | 1/548 (0.2%) | 0/562 (0%) | ||
| Pericardial effusion | 2/548 (0.4%) | 2/562 (0.4%) | ||
| Right ventricular failure | 0/548 (0%) | 1/562 (0.2%) | ||
| Supraventricular tachycardia | 0/548 (0%) | 2/562 (0.4%) | ||
| Tachycardia | 0/548 (0%) | 1/562 (0.2%) | ||
| Tricuspid valve incompetence | 0/548 (0%) | 1/562 (0.2%) | ||
| Ventricular fibrillation | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Congenital, familial and genetic disorders | ||||
| Tracheo-oesophageal fistula | 1/548 (0.2%) | 0/562 (0%) | ||
| Ear and labyrinth disorders | ||||
| Deafness | 0/548 (0%) | 1/562 (0.2%) | ||
| Vertigo | 0/548 (0%) | 1/562 (0.2%) | ||
| Eye disorders | ||||
| Retinal detachment | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 1/548 (0.2%) | 0/562 (0%) | ||
| Abdominal pain | 6/548 (1.1%) | 8/562 (1.4%) | ||
| Abdominal pain upper | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Anal ulcer | 1/548 (0.2%) | 0/562 (0%) | ||
| Colitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Constipation | 5/548 (0.9%) | 6/562 (1.1%) | ||
| Diarrhoea | 8/548 (1.5%) | 5/562 (0.9%) | ||
| Dyspepsia | 1/548 (0.2%) | 0/562 (0%) | ||
| Dysphagia | 2/548 (0.4%) | 0/562 (0%) | ||
| Enteritis | 1/548 (0.2%) | 0/562 (0%) | ||
| Faecaloma | 0/548 (0%) | 1/562 (0.2%) | ||
| Gastric ulcer | 1/548 (0.2%) | 0/562 (0%) | ||
| Gastrointestinal haemorrhage | 0/548 (0%) | 2/562 (0.4%) | ||
| Haematemesis | 2/548 (0.4%) | 0/562 (0%) | ||
| Ileus paralytic | 1/548 (0.2%) | 0/562 (0%) | ||
| Intestinal obstruction | 1/548 (0.2%) | 0/562 (0%) | ||
| Intestinal perforation | 1/548 (0.2%) | 0/562 (0%) | ||
| Melaena | 0/548 (0%) | 1/562 (0.2%) | ||
| Nausea | 6/548 (1.1%) | 5/562 (0.9%) | ||
| Odynophagia | 1/548 (0.2%) | 0/562 (0%) | ||
| Oesophagitis | 3/548 (0.5%) | 1/562 (0.2%) | ||
| Vomiting | 16/548 (2.9%) | 14/562 (2.5%) | ||
| General disorders | ||||
| Asthenia | 4/548 (0.7%) | 2/562 (0.4%) | ||
| Chest discomfort | 0/548 (0%) | 2/562 (0.4%) | ||
| Chest pain | 7/548 (1.3%) | 6/562 (1.1%) | ||
| Death | 2/548 (0.4%) | 0/562 (0%) | ||
| Drug interaction | 1/548 (0.2%) | 0/562 (0%) | ||
| Fatigue | 5/548 (0.9%) | 2/562 (0.4%) | ||
| Gait disturbance | 0/548 (0%) | 1/562 (0.2%) | ||
| General physical health deterioration | 22/548 (4%) | 4/562 (0.7%) | ||
| Injection site reaction | 1/548 (0.2%) | 0/562 (0%) | ||
| Malaise | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Mucosal inflammation | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Multi-organ failure | 0/548 (0%) | 1/562 (0.2%) | ||
| Oedema | 1/548 (0.2%) | 0/562 (0%) | ||
| Pain | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Performance status decreased | 0/548 (0%) | 1/562 (0.2%) | ||
| Pyrexia | 16/548 (2.9%) | 6/562 (1.1%) | ||
| Sudden death | 2/548 (0.4%) | 0/562 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic pain | 1/548 (0.2%) | 0/562 (0%) | ||
| Hyperbilirubinaemia | 2/548 (0.4%) | 0/562 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic reaction | 3/548 (0.5%) | 0/562 (0%) | ||
| Anaphylactic shock | 2/548 (0.4%) | 0/562 (0%) | ||
| Drug hypersensitivity | 1/548 (0.2%) | 0/562 (0%) | ||
| Hypersensitivity | 5/548 (0.9%) | 1/562 (0.2%) | ||
| Serum sickness | 1/548 (0.2%) | 0/562 (0%) | ||
| Infections and infestations | ||||
| Anal abscess | 0/548 (0%) | 1/562 (0.2%) | ||
| Bacteraemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Bacterial sepsis | 0/548 (0%) | 1/562 (0.2%) | ||
| Brain abscess | 1/548 (0.2%) | 0/562 (0%) | ||
| Bronchitis | 2/548 (0.4%) | 2/562 (0.4%) | ||
| Bronchitis bacterial | 1/548 (0.2%) | 0/562 (0%) | ||
| Bronchopneumonia | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Catheter related infection | 3/548 (0.5%) | 0/562 (0%) | ||
| Cellulitis | 4/548 (0.7%) | 0/562 (0%) | ||
| Central line infection | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Clostridial infection | 0/548 (0%) | 1/562 (0.2%) | ||
| Clostridium difficile colitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Dengue fever | 0/548 (0%) | 1/562 (0.2%) | ||
| Diverticulitis | 0/548 (0%) | 1/562 (0.2%) | ||
| Febrile infection | 2/548 (0.4%) | 0/562 (0%) | ||
| Gangrene | 1/548 (0.2%) | 0/562 (0%) | ||
| Gastroenteritis | 0/548 (0%) | 1/562 (0.2%) | ||
| Infection | 3/548 (0.5%) | 1/562 (0.2%) | ||
| Laryngitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Laryngotracheo bronchitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Lobar pneumonia | 1/548 (0.2%) | 0/562 (0%) | ||
| Lower respiratory tract infection | 4/548 (0.7%) | 2/562 (0.4%) | ||
| Lung abscess | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Lung infection | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Nasopharyngitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Neutropenic infection | 9/548 (1.6%) | 5/562 (0.9%) | ||
| Neutropenic sepsis | 9/548 (1.6%) | 5/562 (0.9%) | ||
| Parotitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Peritonsillar abscess | 0/548 (0%) | 1/562 (0.2%) | ||
| Pharyngitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Pharyngotonsillitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Pneumonia | 19/548 (3.5%) | 13/562 (2.3%) | ||
| Pneumonia necrotising | 1/548 (0.2%) | 0/562 (0%) | ||
| Pneumonia streptococcal | 1/548 (0.2%) | 0/562 (0%) | ||
| Postoperative wound infection | 0/548 (0%) | 1/562 (0.2%) | ||
| Pulmonary tuberculosis | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Pyothorax | 1/548 (0.2%) | 0/562 (0%) | ||
| Respiratory tract infection | 2/548 (0.4%) | 2/562 (0.4%) | ||
| Sepsis | 9/548 (1.6%) | 3/562 (0.5%) | ||
| Septic shock | 6/548 (1.1%) | 0/562 (0%) | ||
| Staphylococcal infection | 1/548 (0.2%) | 0/562 (0%) | ||
| Staphylococcal sepsis | 1/548 (0.2%) | 0/562 (0%) | ||
| Urinary tract infection | 1/548 (0.2%) | 0/562 (0%) | ||
| Wound infection | 1/548 (0.2%) | 0/562 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Femoral neck fracture | 1/548 (0.2%) | 0/562 (0%) | ||
| Femur fracture | 1/548 (0.2%) | 0/562 (0%) | ||
| Lumbar vertebral fracture | 2/548 (0.4%) | 0/562 (0%) | ||
| Overdose | 0/548 (0%) | 1/562 (0.2%) | ||
| Investigations | ||||
| Aspiration bronchial | 1/548 (0.2%) | 0/562 (0%) | ||
| Blood creatinine increased | 5/548 (0.9%) | 4/562 (0.7%) | ||
| Blood glucose abnormal | 0/548 (0%) | 1/562 (0.2%) | ||
| Blood potassium decreased | 0/548 (0%) | 1/562 (0.2%) | ||
| Blood urea increased | 1/548 (0.2%) | 0/562 (0%) | ||
| C-reactive protein increased | 2/548 (0.4%) | 0/562 (0%) | ||
| Karnofsky scale worsened | 1/548 (0.2%) | 0/562 (0%) | ||
| Neutrophil count decreased | 1/548 (0.2%) | 0/562 (0%) | ||
| Pulmonary arterial pressure increased | 0/548 (0%) | 1/562 (0.2%) | ||
| Weight decreased | 0/548 (0%) | 1/562 (0.2%) | ||
| White blood cell count decreased | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 4/548 (0.7%) | 2/562 (0.4%) | ||
| Dehydration | 12/548 (2.2%) | 9/562 (1.6%) | ||
| Diabetes mellitus | 1/548 (0.2%) | 0/562 (0%) | ||
| Fluid overload | 0/548 (0%) | 1/562 (0.2%) | ||
| Hypercreatininaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Hyperglycaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Hyperkalaemia | 2/548 (0.4%) | 0/562 (0%) | ||
| Hypocalcaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Hypoglycaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Hypokalaemia | 4/548 (0.7%) | 0/562 (0%) | ||
| Hypomagnesaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Hyponatraemia | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Metabolic acidosis | 1/548 (0.2%) | 0/562 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/548 (0.2%) | 0/562 (0%) | ||
| Back pain | 2/548 (0.4%) | 0/562 (0%) | ||
| Bone pain | 0/548 (0%) | 1/562 (0.2%) | ||
| Muscular weakness | 0/548 (0%) | 2/562 (0.4%) | ||
| Musculoskeletal pain | 2/548 (0.4%) | 1/562 (0.2%) | ||
| Neck pain | 1/548 (0.2%) | 0/562 (0%) | ||
| Pathological fracture | 2/548 (0.4%) | 0/562 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant neoplasm progression | 1/548 (0.2%) | 0/562 (0%) | ||
| Metastases to heart | 1/548 (0.2%) | 0/562 (0%) | ||
| Metastases to meninges | 1/548 (0.2%) | 0/562 (0%) | ||
| Neoplasm progression | 1/548 (0.2%) | 0/562 (0%) | ||
| Testis cancer | 1/548 (0.2%) | 0/562 (0%) | ||
| Tumour pain | 2/548 (0.4%) | 0/562 (0%) | ||
| Nervous system disorders | ||||
| Altered state of consciousness | 0/548 (0%) | 1/562 (0.2%) | ||
| Cerebellar syndrome | 0/548 (0%) | 1/562 (0.2%) | ||
| Cerebral artery embolism | 1/548 (0.2%) | 0/562 (0%) | ||
| Cerebral haemorrhage | 0/548 (0%) | 2/562 (0.4%) | ||
| Cerebral infarction | 0/548 (0%) | 2/562 (0.4%) | ||
| Cerebral ischaemia | 3/548 (0.5%) | 0/562 (0%) | ||
| Cerebrovascular accident | 2/548 (0.4%) | 5/562 (0.9%) | ||
| Cognitive disorder | 1/548 (0.2%) | 0/562 (0%) | ||
| Coma | 1/548 (0.2%) | 0/562 (0%) | ||
| Convulsion | 3/548 (0.5%) | 0/562 (0%) | ||
| Coordination abnormal | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Depressed level of consciousness | 0/548 (0%) | 1/562 (0.2%) | ||
| Dizziness | 2/548 (0.4%) | 0/562 (0%) | ||
| Dysarthria | 0/548 (0%) | 1/562 (0.2%) | ||
| Embolic cerebral infarction | 0/548 (0%) | 1/562 (0.2%) | ||
| Epilepsy | 0/548 (0%) | 1/562 (0.2%) | ||
| Headache | 1/548 (0.2%) | 0/562 (0%) | ||
| Hemiparesis | 0/548 (0%) | 1/562 (0.2%) | ||
| Hemiplegia | 1/548 (0.2%) | 0/562 (0%) | ||
| Horner's syndrome | 1/548 (0.2%) | 0/562 (0%) | ||
| Monoparesis | 1/548 (0.2%) | 0/562 (0%) | ||
| Nervous system disorder | 0/548 (0%) | 1/562 (0.2%) | ||
| Neuralgia | 1/548 (0.2%) | 0/562 (0%) | ||
| Paraparesis | 0/548 (0%) | 2/562 (0.4%) | ||
| Paraplegia | 0/548 (0%) | 1/562 (0.2%) | ||
| Somnolence | 1/548 (0.2%) | 0/562 (0%) | ||
| Speech disorder | 2/548 (0.4%) | 0/562 (0%) | ||
| Spinal cord compression | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Syncope | 1/548 (0.2%) | 2/562 (0.4%) | ||
| Syncope vasovagal | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Transverse sinus thrombosis | 1/548 (0.2%) | 0/562 (0%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/548 (0%) | 1/562 (0.2%) | ||
| Confusional state | 5/548 (0.9%) | 4/562 (0.7%) | ||
| Depression | 0/548 (0%) | 1/562 (0.2%) | ||
| Hallucination | 0/548 (0%) | 1/562 (0.2%) | ||
| Mental disorder | 0/548 (0%) | 1/562 (0.2%) | ||
| Renal and urinary disorders | ||||
| Renal colic | 1/548 (0.2%) | 0/562 (0%) | ||
| Renal failure | 6/548 (1.1%) | 6/562 (1.1%) | ||
| Renal failure acute | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Renal impairment | 2/548 (0.4%) | 0/562 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/548 (0.2%) | 0/562 (0%) | ||
| Acute respiratory distress syndrome | 1/548 (0.2%) | 0/562 (0%) | ||
| Acute respiratory failure | 0/548 (0%) | 1/562 (0.2%) | ||
| Apnoea | 2/548 (0.4%) | 0/562 (0%) | ||
| Cough | 0/548 (0%) | 1/562 (0.2%) | ||
| Dyspnoea | 18/548 (3.3%) | 13/562 (2.3%) | ||
| Haemoptysis | 3/548 (0.5%) | 6/562 (1.1%) | ||
| Hypoxia | 0/548 (0%) | 2/562 (0.4%) | ||
| Lung infiltration | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Pleural effusion | 2/548 (0.4%) | 4/562 (0.7%) | ||
| Pneumonitis | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Pneumothorax | 1/548 (0.2%) | 3/562 (0.5%) | ||
| Pulmonary embolism | 20/548 (3.6%) | 13/562 (2.3%) | ||
| Pulmonary haemorrhage | 1/548 (0.2%) | 2/562 (0.4%) | ||
| Pulmonary oedema | 1/548 (0.2%) | 2/562 (0.4%) | ||
| Respiratory distress | 1/548 (0.2%) | 0/562 (0%) | ||
| Respiratory failure | 14/548 (2.6%) | 9/562 (1.6%) | ||
| Respiratory tract haemorrhage | 0/548 (0%) | 1/562 (0.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 1/548 (0.2%) | 0/562 (0%) | ||
| Rash | 4/548 (0.7%) | 0/562 (0%) | ||
| Rash maculo-papular | 1/548 (0.2%) | 0/562 (0%) | ||
| Vascular disorders | ||||
| Arterial occlusive disease | 0/548 (0%) | 2/562 (0.4%) | ||
| Arterial thrombosis | 1/548 (0.2%) | 0/562 (0%) | ||
| Axillary vein thrombosis | 1/548 (0.2%) | 0/562 (0%) | ||
| Deep vein thrombosis | 9/548 (1.6%) | 3/562 (0.5%) | ||
| Embolism | 0/548 (0%) | 1/562 (0.2%) | ||
| Haematoma | 1/548 (0.2%) | 0/562 (0%) | ||
| Hypertension | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Hypertensive crisis | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Hypotension | 5/548 (0.9%) | 0/562 (0%) | ||
| Iliac artery occlusion | 1/548 (0.2%) | 0/562 (0%) | ||
| Jugular vein thrombosis | 0/548 (0%) | 1/562 (0.2%) | ||
| Pelvic venous thrombosis | 1/548 (0.2%) | 0/562 (0%) | ||
| Peripheral ischaemia | 1/548 (0.2%) | 0/562 (0%) | ||
| Phlebitis | 0/548 (0%) | 2/562 (0.4%) | ||
| Shock | 1/548 (0.2%) | 0/562 (0%) | ||
| Superior vena caval occlusion | 1/548 (0.2%) | 2/562 (0.4%) | ||
| Thrombosis | 2/548 (0.4%) | 2/562 (0.4%) | ||
| Varicose vein | 0/548 (0%) | 1/562 (0.2%) | ||
| Vascular fragility | 0/548 (0%) | 1/562 (0.2%) | ||
| Vasculitis | 1/548 (0.2%) | 0/562 (0%) | ||
| Vena cava thrombosis | 0/548 (0%) | 1/562 (0.2%) | ||
| Venous thrombosis | 1/548 (0.2%) | 1/562 (0.2%) | ||
| Visceral arterial ischaemia | 1/548 (0.2%) | 0/562 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cetuximab Plus Chemotherapy | Chemotherapy Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 532/548 (97.1%) | 537/562 (95.6%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 302/548 (55.1%) | 324/562 (57.7%) | ||
| Anaemia | 226/548 (41.2%) | 264/562 (47%) | ||
| Leukopenia | 176/548 (32.1%) | 155/562 (27.6%) | ||
| Febrile neutropenia | 36/548 (6.6%) | 32/562 (5.7%) | ||
| Thrombocytopenia | 23/548 (4.2%) | 30/562 (5.3%) | ||
| Ear and labyrinth disorders | ||||
| Tinnitus | 49/548 (8.9%) | 55/562 (9.8%) | ||
| Eye disorders | ||||
| Conjunctivitis | 33/548 (6%) | 6/562 (1.1%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 291/548 (53.1%) | 303/562 (53.9%) | ||
| Vomiting | 214/548 (39.1%) | 225/562 (40%) | ||
| Constipation | 204/548 (37.2%) | 189/562 (33.6%) | ||
| Diarrhoea | 126/548 (23%) | 103/562 (18.3%) | ||
| Stomatitis | 85/548 (15.5%) | 27/562 (4.8%) | ||
| Abdominal pain | 72/548 (13.1%) | 72/562 (12.8%) | ||
| Dyspepsia | 68/548 (12.4%) | 55/562 (9.8%) | ||
| Abdominal pain upper | 45/548 (8.2%) | 37/562 (6.6%) | ||
| Dysphagia | 31/548 (5.7%) | 7/562 (1.2%) | ||
| General disorders | ||||
| Fatigue | 202/548 (36.9%) | 181/562 (32.2%) | ||
| Pyrexia | 112/548 (20.4%) | 80/562 (14.2%) | ||
| Asthenia | 90/548 (16.4%) | 96/562 (17.1%) | ||
| Chest pain | 70/548 (12.8%) | 70/562 (12.5%) | ||
| Mucosal inflammation | 56/548 (10.2%) | 23/562 (4.1%) | ||
| Chills | 35/548 (6.4%) | 19/562 (3.4%) | ||
| Injection site reaction | 33/548 (6%) | 29/562 (5.2%) | ||
| Oedema peripheral | 29/548 (5.3%) | 39/562 (6.9%) | ||
| Infections and infestations | ||||
| Paronychia | 46/548 (8.4%) | 0/562 (0%) | ||
| Nasopharyngitis | 37/548 (6.8%) | 16/562 (2.8%) | ||
| Investigations | ||||
| Weight decreased | 75/548 (13.7%) | 50/562 (8.9%) | ||
| Blood creatinine increased | 47/548 (8.6%) | 49/562 (8.7%) | ||
| White blood cell count decreased | 36/548 (6.6%) | 26/562 (4.6%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 208/548 (38%) | 202/562 (35.9%) | ||
| Hypokalaemia | 75/548 (13.7%) | 49/562 (8.7%) | ||
| Hypomagnesaemia | 54/548 (9.9%) | 27/562 (4.8%) | ||
| Hypocalcaemia | 31/548 (5.7%) | 10/562 (1.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 53/548 (9.7%) | 32/562 (5.7%) | ||
| Back pain | 39/548 (7.1%) | 44/562 (7.8%) | ||
| Myalgia | 39/548 (7.1%) | 37/562 (6.6%) | ||
| Arthralgia | 30/548 (5.5%) | 22/562 (3.9%) | ||
| Bone pain | 29/548 (5.3%) | 28/562 (5%) | ||
| Nervous system disorders | ||||
| Dizziness | 82/548 (15%) | 57/562 (10.1%) | ||
| Headache | 79/548 (14.4%) | 60/562 (10.7%) | ||
| Peripheral sensory neuropathy | 49/548 (8.9%) | 46/562 (8.2%) | ||
| Paraesthesia | 40/548 (7.3%) | 27/562 (4.8%) | ||
| Dysgeusia | 31/548 (5.7%) | 33/562 (5.9%) | ||
| Psychiatric disorders | ||||
| Insomnia | 58/548 (10.6%) | 49/562 (8.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 101/548 (18.4%) | 95/562 (16.9%) | ||
| Cough | 97/548 (17.7%) | 80/562 (14.2%) | ||
| Haemoptysis | 45/548 (8.2%) | 24/562 (4.3%) | ||
| Dysphonia | 33/548 (6%) | 14/562 (2.5%) | ||
| Pharyngolaryngeal pain | 31/548 (5.7%) | 20/562 (3.6%) | ||
| Epistaxis | 30/548 (5.5%) | 15/562 (2.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 249/548 (45.4%) | 17/562 (3%) | ||
| Alopecia | 107/548 (19.5%) | 107/562 (19%) | ||
| Dry skin | 76/548 (13.9%) | 9/562 (1.6%) | ||
| Dermatitis acneiform | 75/548 (13.7%) | 1/562 (0.2%) | ||
| Pruritus | 64/548 (11.7%) | 13/562 (2.3%) | ||
| Acne | 38/548 (6.9%) | 2/562 (0.4%) | ||
| Skin fissures | 30/548 (5.5%) | 0/562 (0%) | ||
| Vascular disorders | ||||
| Phlebitis | 48/548 (8.8%) | 44/562 (7.8%) | ||
| Hypertension | 40/548 (7.3%) | 27/562 (4.8%) | ||
| Hypotension | 39/548 (7.1%) | 23/562 (4.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Merck KGaA Communication Center |
|---|---|
| Organization | Merck KGaA |
| Phone | +49-6151-72-5200 |
| service@merckgroup.com |
Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT00148798
Other Study ID Numbers:
- EMR 62202-046
First Posted:
Sep 8, 2005
Last Update Posted:
Jun 25, 2014
Last Verified:
Jun 1, 2014