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Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer (EXPAND)

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ClinicalTrials.gov Identifier: NCT00678535
Recruitment Status : Completed
First Posted : May 15, 2008
Results First Posted : May 16, 2013
Last Update Posted : July 21, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastric Cancer
Interventions Drug: Cetuximab
Drug: Capecitabine
Drug: Cisplatin
Enrollment 904
Recruitment Details First/last participant (informed consent): June 2008/December 2010. Clinical data cut-off: 31 March 2012 Study completion 17 February 2013.
Pre-assignment Details Enrolled: 1,191 screened for eligibility; 287 excluded (mainly non-fulfillment of inclusion or exclusion criteria). 904 participants randomized.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent. Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Period Title: Overall Study
Started 455 [1] 449 [1]
Completed 362 [2] 351 [2]
Not Completed 93 98
[1]
ITT population
[2]
subjects who died before or at 31 March 2012
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin Total
Hide Arm/Group Description Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent. Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 455 449 904
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 455 participants 449 participants 904 participants
58.0  (11.16) 58.5  (10.83) 58.3  (11.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 455 participants 449 participants 904 participants
Female
116
  25.5%
115
  25.6%
231
  25.6%
Male
339
  74.5%
334
  74.4%
673
  74.4%
1.Primary Outcome
Title Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
Hide Description The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants 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 participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized to trial treatment.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 455 449
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(4.2 to 5.5)
5.6
(5.1 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus Capecitabine Plus Cisplatin, Capecitabine Plus Cisplatin
Comments Primary efficacy analysis: To test equality of progression free survival time between treatment groups, applying the two-sided stratified log-rank test (randomization strata: disease stage, previous oesophagectomy/gastrectomy and prior(neo-) adjuvant(radio) chemotherapy, α=5%).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3158
Comments [Not Specified]
Method Stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.091
Confidence Interval 95%
0.920 to 1.292
Estimation Comments Kaplan-Meier method was used to estimate median PFS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description The OS time is defined as the time from randomization to death or last day known to be alive. Participants 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 randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to trial treatment.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 455 449
Median (95% Confidence Interval)
Unit of Measure: months
9.4
(8.3 to 10.6)
10.7
(9.4 to 11.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus Capecitabine Plus Cisplatin, Capecitabine Plus Cisplatin
Comments To test equality of OS time between treatment groups, applying the two-sided stratified log-rank test (randomization strata: disease stage, previous oesophagectomy/gastrectomy and prior (neo-) adjuvant(radio) chemotherapy, α=5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9547
Comments [Not Specified]
Method Stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.004
Confidence Interval 95%
0.866 to 1.165
Estimation Comments Kaplan-Meier method was used to estimate median OS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.
3.Secondary Outcome
Title Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments
Hide Description The BOR rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the best overall response, based on radiological assessments (based on response evaluation criteria in solid tumors [RECIST] Version 1.0) from the IRC.
Time Frame Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to trial treatment.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 455 449
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
29.9
(25.7 to 34.3)
29.2
(25.0 to 33.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab Plus Capecitabine Plus Cisplatin, Capecitabine Plus Cisplatin
Comments The best overall response rate was compared with the Cochran-Mantel-Haenszel test (strata: disease stage, previous oesophagectomy/gastrectomy and prior(neo-) adjuvant(radio) chemotherapy, two-sided with α=5%).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7696
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0435
Confidence Interval 95%
0.7844 to 1.3882
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Hide Description Mean global health status and 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 better QoL.
Time Frame Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included participants who had at least one evaluable EORTC QLQ-C30 questionnaire and were also included in the ITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 450 430
Mean (Standard Deviation)
Unit of Measure: units on a scale
Global health status: Baseline 57.49  (22.168) 57.19  (22.124)
Global health status: Week 6 59.00  (21.879) 61.80  (22.089)
Global health status: Week 12 60.17  (20.796) 63.35  (22.077)
Global health status: Week 18 60.45  (20.015) 61.83  (21.499)
Global health status: Week 24 62.46  (22.978) 63.61  (19.477)
Global health status: Week 30 63.65  (21.722) 64.11  (19.757)
Global health status: Week 36 65.06  (22.629) 57.72  (21.602)
Global health status: Week 42 59.29  (21.558) 62.64  (22.005)
Global health status: Week 48 63.39  (21.317) 66.67  (19.395)
Global health status: Week 54 60.63  (16.198) 66.67  (14.651)
Global health status: Week 60 62.50  (13.918) 61.81  (17.210)
Social functioning status: Baseline 74.36  (27.077) 76.52  (26.601)
Social functioning status: Week 6 68.94  (28.885) 75.70  (27.415)
Social functioning status: Week 12 71.48  (26.547) 75.65  (27.691)
Social functioning status: Week 18 71.22  (25.317) 75.51  (25.612)
Social functioning status: Week 24 74.20  (26.143) 78.26  (27.633)
Social functioning status: Week 30 78.51  (24.766) 76.67  (24.962)
Social functioning status: Week 36 76.28  (21.730) 73.58  (22.353)
Social functioning status: Week 42 68.57  (27.348) 78.16  (22.318)
Social functioning status at Week 48 80.36  (22.705) 78.00  (23.432)
Social functioning status: Week 54 74.71  (27.682) 80.56  (27.371)
Social functioning status: Week 60 78.33  (23.632) 68.06  (32.144)
5.Secondary Outcome
Title Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire
Hide Description EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 single items are combined to obtain a single index score that is health utility index (HUI) score reflecting subject's preferences for different health states. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QoL.
Time Frame Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included participants who had at least one evaluable EuroQoL EQ-5D questionnaire and were also included in the ITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 450 430
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.743  (0.240) 0.749  (0.235)
Week 6 0.739  (0.276) 0.769  (0.254)
Week 12 0.752  (0.239) 0.775  (0.246)
Week 18 0.742  (0.251) 0.755  (0.235)
Week 24 0.733  (0.300) 0.761  (0.265)
Week 30 0.737  (0.301) 0.790  (0.230)
Week 36 0.710  (0.311) 0.711  (0.309)
Week 42 0.722  (0.209) 0.689  (0.307)
Week 48 0.719  (0.227) 0.770  (0.216)
Week 54 0.733  (0.275) 0.730  (0.191)
Week 60 0.760  (0.322) 0.742  (0.170)
6.Secondary Outcome
Title Safety - Number of Participants With Adverse Events (AEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
Time Frame Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of any trial treatment that is, cetuximab, cisplatin, or capecitabine.
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description:
Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 446 436
Measure Type: Number
Unit of Measure: participants
446 432
Time Frame Time from first dose up to 30 days after the last dose of study treatment.
Adverse Event Reporting Description An AE is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
 
Arm/Group Title Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Hide Arm/Group Description Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] followed by 250 mg/m^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent. Cisplatin (3-week cycle, 80 mg/m^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent.
All-Cause Mortality
Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Affected / at Risk (%) Affected / at Risk (%)
Total   239/446 (53.59%)   194/436 (44.50%) 
Blood and lymphatic system disorders     
Anaemia  10/446 (2.24%)  17/436 (3.90%) 
Neutropenia  9/446 (2.02%)  13/436 (2.98%) 
Febrile neutropenia  5/446 (1.12%)  5/436 (1.15%) 
Leukopenia  3/446 (0.67%)  7/436 (1.61%) 
Thrombocytopenia  2/446 (0.45%)  6/436 (1.38%) 
Disseminated intravascular coagulation  1/446 (0.22%)  0/436 (0.00%) 
Granulocytopenia  0/446 (0.00%)  1/436 (0.23%) 
Cardiac disorders     
Acute myocardial infarction  4/446 (0.90%)  2/436 (0.46%) 
Cardiac arrest  3/446 (0.67%)  1/436 (0.23%) 
Myocardial infarction  3/446 (0.67%)  2/436 (0.46%) 
Atrial fibrillation  2/446 (0.45%)  2/436 (0.46%) 
Cardio-respiratory arrest  2/446 (0.45%)  4/436 (0.92%) 
Myocardial ischaemia  2/446 (0.45%)  3/436 (0.69%) 
Acute coronary syndrome  1/446 (0.22%)  0/436 (0.00%) 
Angina pectoris  1/446 (0.22%)  0/436 (0.00%) 
Atrial flutter  1/446 (0.22%)  0/436 (0.00%) 
Cardiac failure  1/446 (0.22%)  0/436 (0.00%) 
Cardiopulmonary failure  1/446 (0.22%)  1/436 (0.23%) 
Intracardiac thrombus  1/446 (0.22%)  1/436 (0.23%) 
Sick sinus syndrome  1/446 (0.22%)  0/436 (0.00%) 
Tachycardia  1/446 (0.22%)  0/436 (0.00%) 
Ventricular extrasystoles  1/446 (0.22%)  0/436 (0.00%) 
Cardiomyopathy  0/446 (0.00%)  1/436 (0.23%) 
Sinus tachycardia  0/446 (0.00%)  1/436 (0.23%) 
Congenital, familial and genetic disorders     
Pyloric stenosis  1/446 (0.22%)  0/436 (0.00%) 
Ear and labyrinth disorders     
Auricular perichondritis  1/446 (0.22%)  0/436 (0.00%) 
Vertigo  1/446 (0.22%)  1/436 (0.23%) 
Endocrine disorders     
Adrenal insufficiency  0/446 (0.00%)  1/436 (0.23%) 
Hyperthyroidism  0/446 (0.00%)  1/436 (0.23%) 
Eye disorders     
Ocular icterus  0/446 (0.00%)  1/436 (0.23%) 
Gastrointestinal disorders     
Vomiting  16/446 (3.59%)  25/436 (5.73%) 
Diarrhoea  15/446 (3.36%)  15/436 (3.44%) 
Nausea  11/446 (2.47%)  13/436 (2.98%) 
Abdominal pain  9/446 (2.02%)  6/436 (1.38%) 
Ascites  9/446 (2.02%)  3/436 (0.69%) 
Dysphagia  6/446 (1.35%)  3/436 (0.69%) 
Ileus  4/446 (0.90%)  7/436 (1.61%) 
Abdominal pain upper  3/446 (0.67%)  2/436 (0.46%) 
Intestinal obstruction  3/446 (0.67%)  3/436 (0.69%) 
Obstruction gastric  3/446 (0.67%)  2/436 (0.46%) 
Subileus  3/446 (0.67%)  1/436 (0.23%) 
Melaena  2/446 (0.45%)  1/436 (0.23%) 
Upper gastrointestinal haemorrhage  2/446 (0.45%)  2/436 (0.46%) 
Abdominal distension  1/446 (0.22%)  0/436 (0.00%) 
Abdominal pain lower  1/446 (0.22%)  1/436 (0.23%) 
Constipation  1/446 (0.22%)  5/436 (1.15%) 
Gastric perforation  1/446 (0.22%)  1/436 (0.23%) 
Gastric stenosis  1/446 (0.22%)  0/436 (0.00%) 
Gastrointestinal obstruction  1/446 (0.22%)  0/436 (0.00%) 
Intestinal perforation  1/446 (0.22%)  1/436 (0.23%) 
Oesophageal perforation  1/446 (0.22%)  0/436 (0.00%) 
Pneumatosis intestinalis  1/446 (0.22%)  1/436 (0.23%) 
Colonic polyp  0/446 (0.00%)  1/436 (0.23%) 
Erosive oesophagitis  0/446 (0.00%)  1/436 (0.23%) 
Gastric haemorrhage  0/446 (0.00%)  2/436 (0.46%) 
Gastrointestinal haemorrhage  0/446 (0.00%)  2/436 (0.46%) 
Gastrointestinal stenosis  0/446 (0.00%)  2/436 (0.46%) 
Haematemesis  0/446 (0.00%)  1/436 (0.23%) 
Haemorrhoids  0/446 (0.00%)  1/436 (0.23%) 
Ileus paralytic  0/446 (0.00%)  1/436 (0.23%) 
Inguinal hernia  0/446 (0.00%)  1/436 (0.23%) 
Mechanical ileus  0/446 (0.00%)  1/436 (0.23%) 
Small intestinal obstruction  0/446 (0.00%)  1/436 (0.23%) 
Stomatitis  0/446 (0.00%)  1/436 (0.23%) 
General disorders     
General physical health deterioration  12/446 (2.69%)  13/436 (2.98%) 
Fatigue  11/446 (2.47%)  5/436 (1.15%) 
Pyrexia  8/446 (1.79%)  7/436 (1.61%) 
Disease progression  7/446 (1.57%)  1/436 (0.23%) 
Asthenia  6/446 (1.35%)  5/436 (1.15%) 
Mucosal inflammation  3/446 (0.67%)  3/436 (0.69%) 
Performance status decreased  3/446 (0.67%)  3/436 (0.69%) 
Device dislocation  2/446 (0.45%)  2/436 (0.46%) 
Non-cardiac chest pain  2/446 (0.45%)  0/436 (0.00%) 
Oedema peripheral  2/446 (0.45%)  0/436 (0.00%) 
Device occlusion  1/446 (0.22%)  0/436 (0.00%) 
Stent malfunction  1/446 (0.22%)  0/436 (0.00%) 
Sudden death  1/446 (0.22%)  0/436 (0.00%) 
Chest discomfort  0/446 (0.00%)  1/436 (0.23%) 
Death  0/446 (0.00%)  2/436 (0.46%) 
Multi-organ failure  0/446 (0.00%)  4/436 (0.92%) 
Pain  0/446 (0.00%)  1/436 (0.23%) 
Hepatobiliary disorders     
Jaundice cholestatic  3/446 (0.67%)  1/436 (0.23%) 
Bile duct stenosis  2/446 (0.45%)  0/436 (0.00%) 
Cholecystitis  1/446 (0.22%)  1/436 (0.23%) 
Cytolytic hepatitis  1/446 (0.22%)  0/436 (0.00%) 
Hepatic failure  1/446 (0.22%)  0/436 (0.00%) 
Hepatotoxicity  1/446 (0.22%)  0/436 (0.00%) 
Hyperbilirubinaemia  1/446 (0.22%)  0/436 (0.00%) 
Jaundice  1/446 (0.22%)  1/436 (0.23%) 
Hepatic lesion  0/446 (0.00%)  1/436 (0.23%) 
Immune system disorders     
Hypersensitivity  4/446 (0.90%)  0/436 (0.00%) 
Anaphylactic shock  1/446 (0.22%)  0/436 (0.00%) 
Infections and infestations     
Sepsis  5/446 (1.12%)  2/436 (0.46%) 
Pneumonia  4/446 (0.90%)  8/436 (1.83%) 
Device related infection  3/446 (0.67%)  4/436 (0.92%) 
Gastroenteritis  3/446 (0.67%)  0/436 (0.00%) 
Septic shock  3/446 (0.67%)  0/436 (0.00%) 
Paronychia  2/446 (0.45%)  0/436 (0.00%) 
Abdominal abscess  1/446 (0.22%)  0/436 (0.00%) 
Bacteraemia  1/446 (0.22%)  0/436 (0.00%) 
Bronchopulmonary aspergillosis  1/446 (0.22%)  0/436 (0.00%) 
Candida sepsis  1/446 (0.22%)  0/436 (0.00%) 
Cellulitis  1/446 (0.22%)  0/436 (0.00%) 
Enterocolitis bacterial  1/446 (0.22%)  0/436 (0.00%) 
Enterocolitis infectious  1/446 (0.22%)  0/436 (0.00%) 
Herpes zoster  1/446 (0.22%)  0/436 (0.00%) 
Infection  1/446 (0.22%)  0/436 (0.00%) 
Klebsiella sepsis  1/446 (0.22%)  0/436 (0.00%) 
Liver abscess  1/446 (0.22%)  0/436 (0.00%) 
Pneumonia bacterial  1/446 (0.22%)  0/436 (0.00%) 
Respiratory tract infection  1/446 (0.22%)  0/436 (0.00%) 
Skin infection  1/446 (0.22%)  0/436 (0.00%) 
Upper respiratory tract infection  1/446 (0.22%)  1/436 (0.23%) 
Bronchitis  0/446 (0.00%)  1/436 (0.23%) 
Cystitis  0/446 (0.00%)  1/436 (0.23%) 
Gangrene  0/446 (0.00%)  1/436 (0.23%) 
Influenza  0/446 (0.00%)  1/436 (0.23%) 
Oesophageal candidiasis  0/446 (0.00%)  1/436 (0.23%) 
Injury, poisoning and procedural complications     
Infusion related reaction  2/446 (0.45%)  0/436 (0.00%) 
Anastomotic stenosis  1/446 (0.22%)  0/436 (0.00%) 
Femur fracture  1/446 (0.22%)  0/436 (0.00%) 
Gastrointestinal stoma complication  1/446 (0.22%)  0/436 (0.00%) 
Upper limb fracture  1/446 (0.22%)  0/436 (0.00%) 
Concussion  0/446 (0.00%)  1/436 (0.23%) 
Fall  0/446 (0.00%)  1/436 (0.23%) 
Laceration  0/446 (0.00%)  1/436 (0.23%) 
Overdose  0/446 (0.00%)  2/436 (0.46%) 
Pneumothorax traumatic  0/446 (0.00%)  1/436 (0.23%) 
Post procedural discharge  0/446 (0.00%)  1/436 (0.23%) 
Road traffic accident  0/446 (0.00%)  1/436 (0.23%) 
Investigations     
Blood bilirubin increased  2/446 (0.45%)  0/436 (0.00%) 
Electrocardiogram QT prolonged  2/446 (0.45%)  0/436 (0.00%) 
Weight decreased  2/446 (0.45%)  1/436 (0.23%) 
Alanine aminotransferase increased  1/446 (0.22%)  1/436 (0.23%) 
Blood creatinine increased  1/446 (0.22%)  5/436 (1.15%) 
Blood urine  1/446 (0.22%)  0/436 (0.00%) 
Electrocardiogram low voltage  1/446 (0.22%)  0/436 (0.00%) 
Glomerular filtration rate decreased  1/446 (0.22%)  0/436 (0.00%) 
International normalised ratio increased  1/446 (0.22%)  0/436 (0.00%) 
Liver function test abnormal  1/446 (0.22%)  0/436 (0.00%) 
Troponin increased  1/446 (0.22%)  0/436 (0.00%) 
Aspartate aminotransferase increased  0/446 (0.00%)  1/436 (0.23%) 
Platelet count decreased  0/446 (0.00%)  1/436 (0.23%) 
Prothrombin time prolonged  0/446 (0.00%)  1/436 (0.23%) 
Troponin I increased  0/446 (0.00%)  2/436 (0.46%) 
Metabolism and nutrition disorders     
Decreased appetite  15/446 (3.36%)  3/436 (0.69%) 
Dehydration  9/446 (2.02%)  15/436 (3.44%) 
Hypokalaemia  7/446 (1.57%)  9/436 (2.06%) 
Hypophagia  3/446 (0.67%)  1/436 (0.23%) 
Cachexia  2/446 (0.45%)  0/436 (0.00%) 
Hypocalcaemia  2/446 (0.45%)  2/436 (0.46%) 
Hypomagnesaemia  2/446 (0.45%)  1/436 (0.23%) 
Hyponatraemia  2/446 (0.45%)  3/436 (0.69%) 
Diabetes mellitus  1/446 (0.22%)  0/436 (0.00%) 
Electrolyte imbalance  1/446 (0.22%)  0/436 (0.00%) 
Malnutrition  1/446 (0.22%)  0/436 (0.00%) 
Hyperglycaemia  0/446 (0.00%)  4/436 (0.92%) 
Hyperkalaemia  0/446 (0.00%)  1/436 (0.23%) 
Hypoglycaemia  0/446 (0.00%)  1/436 (0.23%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1/446 (0.22%)  0/436 (0.00%) 
Back pain  1/446 (0.22%)  0/436 (0.00%) 
Bone pain  1/446 (0.22%)  1/436 (0.23%) 
Muscular weakness  1/446 (0.22%)  0/436 (0.00%) 
Musculoskeletal pain  1/446 (0.22%)  0/436 (0.00%) 
Soft tissue necrosis  1/446 (0.22%)  0/436 (0.00%) 
Spondylitis  1/446 (0.22%)  0/436 (0.00%) 
Musculoskeletal chest pain  0/446 (0.00%)  1/436 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage  3/446 (0.67%)  1/436 (0.23%) 
Metastases to ovary  1/446 (0.22%)  0/436 (0.00%) 
Neoplasm malignant  1/446 (0.22%)  0/436 (0.00%) 
Tumour pain  1/446 (0.22%)  2/436 (0.46%) 
Tumour perforation  1/446 (0.22%)  1/436 (0.23%) 
Tumour rupture  1/446 (0.22%)  0/436 (0.00%) 
Metastases to central nervous system  0/446 (0.00%)  1/436 (0.23%) 
Metastases to meninges  0/446 (0.00%)  1/436 (0.23%) 
Tumour associated fever  0/446 (0.00%)  1/436 (0.23%) 
Nervous system disorders     
Syncope  6/446 (1.35%)  4/436 (0.92%) 
Cerebral infarction  5/446 (1.12%)  1/436 (0.23%) 
Ischaemic stroke  3/446 (0.67%)  1/436 (0.23%) 
Brain stem infarction  1/446 (0.22%)  0/436 (0.00%) 
Cerebral haemorrhage  1/446 (0.22%)  2/436 (0.46%) 
Cerebral ischaemia  1/446 (0.22%)  0/436 (0.00%) 
Dizziness  1/446 (0.22%)  5/436 (1.15%) 
Headache  1/446 (0.22%)  1/436 (0.23%) 
Hepatic encephalopathy  1/446 (0.22%)  0/436 (0.00%) 
Lumbar radiculopathy  1/446 (0.22%)  0/436 (0.00%) 
Spinal cord compression  1/446 (0.22%)  1/436 (0.23%) 
Cerebrovascular accident  0/446 (0.00%)  1/436 (0.23%) 
Convulsion  0/446 (0.00%)  1/436 (0.23%) 
Depressed level of consciousness  0/446 (0.00%)  1/436 (0.23%) 
Facial paresis  0/446 (0.00%)  1/436 (0.23%) 
Hemiparesis  0/446 (0.00%)  1/436 (0.23%) 
Paraesthesia  0/446 (0.00%)  2/436 (0.46%) 
Presyncope  0/446 (0.00%)  1/436 (0.23%) 
Subarachnoid haemorrhage  0/446 (0.00%)  1/436 (0.23%) 
Psychiatric disorders     
Delirium  1/446 (0.22%)  0/436 (0.00%) 
Depression  1/446 (0.22%)  0/436 (0.00%) 
Completed suicide  0/446 (0.00%)  2/436 (0.46%) 
Renal and urinary disorders     
Renal failure  3/446 (0.67%)  4/436 (0.92%) 
Renal failure acute  2/446 (0.45%)  0/436 (0.00%) 
Acute prerenal failure  1/446 (0.22%)  2/436 (0.46%) 
Calculus ureteric  1/446 (0.22%)  0/436 (0.00%) 
Haematuria  1/446 (0.22%)  0/436 (0.00%) 
Hydronephrosis  1/446 (0.22%)  1/436 (0.23%) 
Renal colic  1/446 (0.22%)  0/436 (0.00%) 
Renal impairment  1/446 (0.22%)  0/436 (0.00%) 
Ureteric obstruction  1/446 (0.22%)  0/436 (0.00%) 
Urinary retention  1/446 (0.22%)  1/436 (0.23%) 
Oliguria  0/446 (0.00%)  1/436 (0.23%) 
Urinary tract obstruction  0/446 (0.00%)  1/436 (0.23%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  0/446 (0.00%)  1/436 (0.23%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  26/446 (5.83%)  13/436 (2.98%) 
Dyspnoea  7/446 (1.57%)  4/436 (0.92%) 
Pleural effusion  4/446 (0.90%)  1/436 (0.23%) 
Bronchospasm  1/446 (0.22%)  0/436 (0.00%) 
Pneumonitis  1/446 (0.22%)  0/436 (0.00%) 
Pneumothorax  1/446 (0.22%)  0/436 (0.00%) 
Pulmonary artery thrombosis  1/446 (0.22%)  0/436 (0.00%) 
Respiratory failure  1/446 (0.22%)  0/436 (0.00%) 
Pulmonary thrombosis  0/446 (0.00%)  1/436 (0.23%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1/446 (0.22%)  0/436 (0.00%) 
Dermatitis acneiform  1/446 (0.22%)  0/436 (0.00%) 
Dry skin  1/446 (0.22%)  0/436 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1/446 (0.22%)  0/436 (0.00%) 
Rash  1/446 (0.22%)  0/436 (0.00%) 
Rash generalised  1/446 (0.22%)  0/436 (0.00%) 
Skin disorder  1/446 (0.22%)  0/436 (0.00%) 
Skin exfoliation  1/446 (0.22%)  0/436 (0.00%) 
Skin toxicity  1/446 (0.22%)  0/436 (0.00%) 
Vascular disorders     
Deep vein thrombosis  11/446 (2.47%)  2/436 (0.46%) 
Hypotension  2/446 (0.45%)  2/436 (0.46%) 
Peripheral ischaemia  2/446 (0.45%)  0/436 (0.00%) 
Circulatory collapse  0/446 (0.00%)  1/436 (0.23%) 
Subclavian vein thrombosis  0/446 (0.00%)  2/436 (0.46%) 
Venous thrombosis  0/446 (0.00%)  1/436 (0.23%) 
Venous thrombosis limb  0/446 (0.00%)  1/436 (0.23%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cetuximab Plus Capecitabine Plus Cisplatin Capecitabine Plus Cisplatin
Affected / at Risk (%) Affected / at Risk (%)
Total   441/446 (98.88%)   429/436 (98.39%) 
Blood and lymphatic system disorders     
Neutropenia  194/446 (43.50%)  234/436 (53.67%) 
Anaemia  127/446 (28.48%)  155/436 (35.55%) 
Thrombocytopenia  81/446 (18.16%)  89/436 (20.41%) 
Leukopenia  67/446 (15.02%)  94/436 (21.56%) 
Ear and labyrinth disorders     
Tinnitus  20/446 (4.48%)  23/436 (5.28%) 
Gastrointestinal disorders     
Nausea  273/446 (61.21%)  265/436 (60.78%) 
Diarrhoea  172/446 (38.57%)  105/436 (24.08%) 
Vomiting  165/446 (37.00%)  192/436 (44.04%) 
Constipation  120/446 (26.91%)  110/436 (25.23%) 
Stomatitis  100/446 (22.42%)  41/436 (9.40%) 
Abdominal pain  92/446 (20.63%)  72/436 (16.51%) 
Abdominal pain upper  67/446 (15.02%)  44/436 (10.09%) 
Dyspepsia  45/446 (10.09%)  21/436 (4.82%) 
Dysphagia  23/446 (5.16%)  14/436 (3.21%) 
General disorders     
Fatigue  187/446 (41.93%)  162/436 (37.16%) 
Asthenia  92/446 (20.63%)  98/436 (22.48%) 
Mucosal inflammation  65/446 (14.57%)  31/436 (7.11%) 
Pyrexia  64/446 (14.35%)  38/436 (8.72%) 
Oedema peripheral  27/446 (6.05%)  26/436 (5.96%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  25/446 (5.61%)  11/436 (2.52%) 
Infections and infestations     
Paronychia  63/446 (14.13%)  3/436 (0.69%) 
Investigations     
Weight decreased  107/446 (23.99%)  77/436 (17.66%) 
Haemoglobin decreased  37/446 (8.30%)  37/436 (8.49%) 
Glomerular filtration rate decreased  30/446 (6.73%)  35/436 (8.03%) 
Blood creatinine increased  29/446 (6.50%)  37/436 (8.49%) 
Aspartate aminotransferase increased  26/446 (5.83%)  13/436 (2.98%) 
Alanine aminotransferase increased  24/446 (5.38%)  16/436 (3.67%) 
Neutrophil count decreased  20/446 (4.48%)  22/436 (5.05%) 
Platelet count decreased  17/446 (3.81%)  22/436 (5.05%) 
Metabolism and nutrition disorders     
Decreased appetite  221/446 (49.55%)  201/436 (46.10%) 
Hypomagnesaemia  133/446 (29.82%)  60/436 (13.76%) 
Hypokalaemia  86/446 (19.28%)  56/436 (12.84%) 
Hypocalcaemia  67/446 (15.02%)  38/436 (8.72%) 
Hyponatraemia  42/446 (9.42%)  34/436 (7.80%) 
Hypoalbuminaemia  39/446 (8.74%)  24/436 (5.50%) 
Dehydration  29/446 (6.50%)  14/436 (3.21%) 
Hypophosphataemia  29/446 (6.50%)  13/436 (2.98%) 
Musculoskeletal and connective tissue disorders     
Back pain  35/446 (7.85%)  19/436 (4.36%) 
Nervous system disorders     
Dizziness  66/446 (14.80%)  45/436 (10.32%) 
Peripheral sensory neuropathy  33/446 (7.40%)  27/436 (6.19%) 
Dysgeusia  32/446 (7.17%)  29/436 (6.65%) 
Headache  31/446 (6.95%)  22/436 (5.05%) 
Neuropathy peripheral  23/446 (5.16%)  41/436 (9.40%) 
Paraesthesia  20/446 (4.48%)  27/436 (6.19%) 
Psychiatric disorders     
Insomnia  41/446 (9.19%)  32/436 (7.34%) 
Respiratory, thoracic and mediastinal disorders     
Cough  38/446 (8.52%)  19/436 (4.36%) 
Dyspnoea  37/446 (8.30%)  21/436 (4.82%) 
Hiccups  29/446 (6.50%)  47/436 (10.78%) 
Skin and subcutaneous tissue disorders     
Rash  194/446 (43.50%)  23/436 (5.28%) 
Palmar-plantar erythrodysaesthesia syndrome  162/446 (36.32%)  97/436 (22.25%) 
Dermatitis acneiform  78/446 (17.49%)  0/436 (0.00%) 
Dry skin  56/446 (12.56%)  11/436 (2.52%) 
Acne  54/446 (12.11%)  1/436 (0.23%) 
Alopecia  28/446 (6.28%)  19/436 (4.36%) 
Skin fissures  28/446 (6.28%)  1/436 (0.23%) 
Skin hyperpigmentation  15/446 (3.36%)  27/436 (6.19%) 
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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merck.de
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00678535    
Other Study ID Numbers: EMR 200048-052
2007-004219-75 ( EudraCT Number )
First Submitted: May 13, 2008
First Posted: May 15, 2008
Results First Submitted: March 30, 2013
Results First Posted: May 16, 2013
Last Update Posted: July 21, 2014