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

• 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: Merck KGaA, Darmstadt, Germany
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Cetuximab Plus Capecitabine Plus Cisplatin	Capecitabine Plus Cisplatin	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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

Adverse Events

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
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	--/--	--/--
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%)
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%)

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA
• Phone: +49-6151-72-5200
• EMail: service@merck.de

• 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