Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00778830
• Collaborator: Merck Pte. Ltd., Singapore (Industry)
• Enrollment: 289
• Location: 1
• Arms: 2
• Duration (Months): 61.9
• Patients Per Site Per Month: 4.7

Study Details

Study Description

Brief Summary

This is an open-label, non-randomized, multicenter Phase II study evaluating folinic acid + fluorouracil + irinotecan (FOLFIRI) plus cetuximab (Erbitux) or folinic acid + fluorouracil + oxaliplatin (FOLFOX) plus cetuximab as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.

Only subjects with k-ras oncogene (KRAS) wild-type tumors are eligible. Efficacy will be assessed every 8 weeks. Treatment will be continued until progressive disease or unacceptable adverse events occur. After the end of study treatment, information on further anticancer treatment and survival will be collected every 3 months.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Cetuximab; Drug: FOLFIRI; Drug: FOLFOX	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 289 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Asia Pacific Non-randomized, Open-label Phase II Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab (Erbitux) or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab plus FOLFIRI	Drug: Cetuximab; Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.; Other Names: Erbitux ; Drug: FOLFIRI; Irinotecan will be administered intravenously at a dose of 180 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil will be administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.
Experimental: Cetuximab plus FOLFOX	Drug: Cetuximab; Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.; Other Names: Erbitux ; Drug: FOLFOX; Oxaliplatin will be administered intravenously at a dose of 100 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil administration intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Best Overall Confirmed Response Rate (BORR) [From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)]

   Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) Time [From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)]

   PFS time was defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 90 days of the last tumor assessment or first study drug dose whichever occurred.

2. Overall Survival (OS) Time [From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)]

   OS time was defined as the time from first administration of study drug until date of death, assessed up to 5 years. OS time was censored if the subject was found to be alive on the last date of the assessment.

3. Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death [From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)]

   An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Signed written informed consent

• Inpatient or outpatient subjects, 18 years of age

• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

• Metastatic disease (M1)

• Life expectancy of at least 12 weeks

• Presence of at least 1 measurable index lesion (not lie in an irradiated area) by computed tomography (CT) scan or magnetic resonance imaging (MRI)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry

• Effective contraception for both male and female subjects if the risk of conception exists

• White blood cell count greater than or equal to (>=) 3,000 per cubic millimeter (/mm^3) with neutrophils >=1,500/mm3, platelet count >=100,000/mm3, hemoglobin >=5.6 millimole per liter (mmol/L) (9 gram per deciliter [g/dL])

• Total bilirubin less than or equal to (<=) 1.5 x upper reference range

• Aspartate aminotransferase (AST) <=2.5 x upper reference range, or <=5 x upper reference range in case of liver metastasis

• Serum creatinine <=1.5 x upper reference range

• Recovery from relevant toxicity to previous treatment before study entry

• KRAS wild-type status of tumor tissue

Exclusion Criteria:

• Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study

• Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study

• Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor (VEGF) therapy, or epidermal growth factor receptor (EGFR-) pathway targeting therapy not indicated in this study protocol

• Concurrent hormone therapy not indicated in this study protocol except for physiologic replacement or contraception

• Known hypersensitivity reaction to any of the components of study treatments

• Pregnancy (absence to be confirmed by beta human choriongonadotrophin [beta-hCG] test) or lactation period

• Brain metastasis and/or leptomeningeal disease (known or suspected)

• Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia

• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

• Peripheral neuropathy > grade 1

• Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix

• Known alcohol or drug abuse

• Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent

• Participation in another clinical study within the past 30 days

• Significant disease which, in the investigator's opinion, would exclude the patient from the study

• Legal incapacity or limited legal capacity

• KRAS mutated status of tumor tissue

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Singapore		Singapore

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany
• Merck Pte. Ltd., Singapore

Investigators

• Study Director: Medical Responsible, Merck Pte. Ltd., Singapore

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT00778830
• Other Study ID Numbers: EMR 62202-505
• First Posted: Oct 23, 2008
• Last Update Posted: May 14, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Merck KGaA, Darmstadt, Germany: mCRC
• Additional relevant MeSH terms: Colorectal Neoplasms; Cetuximab

Study Results

Participant Flow

Recruitment Details	First/Last subject (informed consent): February 2009/June 2012. Study completion date: April 2014. Clinical data cut-off: 31 March 2014. Subjects were recruited in 12 countries (Australia, China, Hong Kong, India, Indonesia, Korea, Malaysia, Singapore, Pakistan, Philippines, Taiwan and Thailand) across the globe in 43 centers.
Pre-assignment Detail	Enrolled: 661 screened for eligibility; 372 were excluded (mainly non-fulfillment of inclusion or exclusion criteria). 289 subjects were assigned to the treatment groups.

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Period Title: Overall Study
STARTED	101	188
COMPLETED	101	187
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX	Total
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Total of all reporting groups
Overall Participants	101	188	289
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	70 69.3%	145 77.1%	215 74.4%
>=65 years	31 30.7%	43 22.9%	74 25.6%
Sex: Female, Male (Count of Participants)
Female	35 34.7%	69 36.7%	104 36%
Male	66 65.3%	119 63.3%	185 64%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)
Description	Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.
Time Frame	From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population consisted of all the enrolled subjects who received at least one dose of study treatment.

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Measure Participants	101	188
Number [Percentage of subjects]	54.5	61.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cetuximab Plus FOLFIRI, Cetuximab Plus FOLFOX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.3176
	Confidence Interval	(2-Sided) 95%; 0.8078 to 2.1491
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-Free Survival (PFS) Time
Description	PFS time was defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 90 days of the last tumor assessment or first study drug dose whichever occurred.
Time Frame	From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all the enrolled subjects who received at least one dose of study treatment.

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Measure Participants	101	188
Median (95% Confidence Interval) [months]	11.1	11.1

3. Secondary Outcome

Title	Overall Survival (OS) Time
Description	OS time was defined as the time from first administration of study drug until date of death, assessed up to 5 years. OS time was censored if the subject was found to be alive on the last date of the assessment.
Time Frame	From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all the enrolled subjects who received at least one dose of study treatment.

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Measure Participants	101	188
Median (95% Confidence Interval) [months]	26.6	27.0

4. Secondary Outcome

Title	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death
Description	An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Outcome Measure Data

Analysis Population Description

Safety population consisted of all the enrolled subjects who received at least one dose of study treatment.

Arm/Group Title	Cetuximab Plus FOLFIRI	Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m^2 ,folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m^2, folinic acid administered intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Measure Participants	101	188
TEAEs	99	180
Treatment Emergent SAEs	37	64
TEAEs Leading to Death	5	10
TEAEs Leading to Discontinuation	0	0

Adverse Events

Time Frame	From the start of the trial treatment up to the data cut-off date (31 March 2014)
Adverse Event Reporting Description	A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Arm/Group Title	Cetuximab Plus FOLFIRI		Cetuximab Plus FOLFOX
Arm/Group Description	Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly until disease progression, death, or consent withdrawal. Irinotecan was administered intravenously at a dose of 180 mg/m^2 along with folinic acid intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.		Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly until disease progression, death, or consent withdrawal. Oxaliplatin was administered intravenously at a dose of 100 mg/m^2 along with folinic acid intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.
All Cause Mortality
	Cetuximab Plus FOLFIRI		Cetuximab Plus FOLFOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cetuximab Plus FOLFIRI		Cetuximab Plus FOLFOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/101 (36.6%)		64/188 (34%)
Blood and lymphatic system disorders
Anaemia	0/101 (0%)		1/188 (0.5%)
Febrile neutropenia	2/101 (2%)		6/188 (3.2%)
Iron deficiency anaemia	1/101 (1%)		0/188 (0%)
Neutropenia	4/101 (4%)		3/188 (1.6%)
Thrombocytopenia	0/101 (0%)		1/188 (0.5%)
Cardiac disorders
Cardio-respiratory arrest	0/101 (0%)		1/188 (0.5%)
Cardiopulmonary failure	1/101 (1%)		0/188 (0%)
Myocardial infarction	1/101 (1%)		1/188 (0.5%)
Palpitations	1/101 (1%)		0/188 (0%)
Supraventricular tachycardia	0/101 (0%)		1/188 (0.5%)
Eye disorders
Vision blurred	1/101 (1%)		0/188 (0%)
Gastrointestinal disorders
Abdominal pain	0/101 (0%)		3/188 (1.6%)
Constipation	0/101 (0%)		2/188 (1.1%)
Diarrhoea	4/101 (4%)		6/188 (3.2%)
Gastritis	0/101 (0%)		1/188 (0.5%)
Haematochezia	0/101 (0%)		1/188 (0.5%)
Ileus	3/101 (3%)		0/188 (0%)
Intestinal obstruction	5/101 (5%)		2/188 (1.1%)
Nausea	0/101 (0%)		1/188 (0.5%)
Rectal Haemorrhage	0/101 (0%)		1/188 (0.5%)
Rectal obstruction	1/101 (1%)		0/188 (0%)
Small intestinal haemorrhage	0/101 (0%)		1/188 (0.5%)
Small intestinal obstruction	0/101 (0%)		1/188 (0.5%)
Stomatitis	0/101 (0%)		1/188 (0.5%)
Vomiting	2/101 (2%)		4/188 (2.1%)
General disorders
Chest discomfort	1/101 (1%)		0/188 (0%)
Death	1/101 (1%)		2/188 (1.1%)
Disease progression	1/101 (1%)		1/188 (0.5%)
Fatigue	0/101 (0%)		1/188 (0.5%)
Multi-organ failure	1/101 (1%)		0/188 (0%)
Pyrexia	3/101 (3%)		7/188 (3.7%)
Hepatobiliary disorders
Bile duct obstruction	0/101 (0%)		1/188 (0.5%)
Cholecystitis	0/101 (0%)		1/188 (0.5%)
Hepatic function abnormal	0/101 (0%)		1/188 (0.5%)
Immune system disorders
Drug hypersensitivity	0/101 (0%)		3/188 (1.6%)
Infections and infestations
Bacteraemia	1/101 (1%)		0/188 (0%)
Biliary sepsis	0/101 (0%)		1/188 (0.5%)
Bronchitis	0/101 (0%)		1/188 (0.5%)
Bronchopneumonia	1/101 (1%)		1/188 (0.5%)
Catheter site infection	0/101 (0%)		3/188 (1.6%)
Cellulitis	1/101 (1%)		0/188 (0%)
Device related infection	0/101 (0%)		1/188 (0.5%)
Escherichia urinary tract infection	0/101 (0%)		1/188 (0.5%)
Gastroenteritis	0/101 (0%)		1/188 (0.5%)
Herpes zoster	0/101 (0%)		1/188 (0.5%)
Infection	1/101 (1%)		0/188 (0%)
Klebsiella sepsis	0/101 (0%)		1/188 (0.5%)
Lower respiratory tract infection	1/101 (1%)		0/188 (0%)
Mycobacterium abscessus infection	0/101 (0%)		1/188 (0.5%)
Nail infection	0/101 (0%)		1/188 (0.5%)
Onychomycosis	0/101 (0%)		1/188 (0.5%)
Paronychia	2/101 (2%)		1/188 (0.5%)
Pneumonia	0/101 (0%)		3/188 (1.6%)
Pneumonia klebsiella	0/101 (0%)		1/188 (0.5%)
Pneumonia viral	0/101 (0%)		1/188 (0.5%)
Sepsis	2/101 (2%)		2/188 (1.1%)
Septic shock	1/101 (1%)		0/188 (0%)
Skin infection	0/101 (0%)		1/188 (0.5%)
Staphylococcal infection	0/101 (0%)		1/188 (0.5%)
Upper respiratory tract infection	0/101 (0%)		2/188 (1.1%)
Urinary tract infection	1/101 (1%)		1/188 (0.5%)
Wound infection	0/101 (0%)		1/188 (0.5%)
Injury, poisoning and procedural complications
Contusion	0/101 (0%)		1/188 (0.5%)
Infusion related reaction	0/101 (0%)		1/188 (0.5%)
Overdose	1/101 (1%)		1/188 (0.5%)
Investigations
Blood bilirubin increased	0/101 (0%)		1/188 (0.5%)
Blood creatinine increased	0/101 (0%)		1/188 (0.5%)
Metabolism and nutrition disorders
Acidosis	0/101 (0%)		1/188 (0.5%)
Dehydration	0/101 (0%)		3/188 (1.6%)
Diabetic ketoacidosis	2/101 (2%)		0/188 (0%)
Hyperglycaemia	0/101 (0%)		1/188 (0.5%)
Hypokalaemia	3/101 (3%)		4/188 (2.1%)
Hypomagnesaemia	1/101 (1%)		1/188 (0.5%)
Hyponatraemia	0/101 (0%)		1/188 (0.5%)
Hypophosphataemia	1/101 (1%)		0/188 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/101 (1%)		0/188 (0%)
Bone pain	1/101 (1%)		0/188 (0%)
Pain in extremity	0/101 (0%)		1/188 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	0/101 (0%)		1/188 (0.5%)
Tumor perforation	0/101 (0%)		1/188 (0.5%)
Nervous system disorders
Convulsion	1/101 (1%)		2/188 (1.1%)
Dizziness	0/101 (0%)		1/188 (0.5%)
Paraesthesia	0/101 (0%)		2/188 (1.1%)
Psychiatric disorders
Confusional state	0/101 (0%)		1/188 (0.5%)
Renal and urinary disorders
Haematuria	1/101 (1%)		0/188 (0%)
Hydronephrosis	1/101 (1%)		0/188 (0%)
Proteinuria	1/101 (1%)		0/188 (0%)
Renal failure acute	1/101 (1%)		1/188 (0.5%)
Reproductive system and breast disorders
Pelvic fluid collection	0/101 (0%)		1/188 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dysaesthesia pharynx	0/101 (0%)		1/188 (0.5%)
Dyspnoea	0/101 (0%)		1/188 (0.5%)
Interstitial lung disease	0/101 (0%)		1/188 (0.5%)
Lung consolidation	0/101 (0%)		1/188 (0.5%)
Pneumothorax	0/101 (0%)		1/188 (0.5%)
Pulmonary embolism	1/101 (1%)		3/188 (1.6%)
Respiratory distress	1/101 (1%)		1/188 (0.5%)
Skin and subcutaneous tissue disorders
Acne	1/101 (1%)		0/188 (0%)
Eczema	0/101 (0%)		1/188 (0.5%)
Hyperhidrosis	1/101 (1%)		0/188 (0%)
Vascular disorders
Deep vein thrombosis	3/101 (3%)		1/188 (0.5%)
Hypotension	0/101 (0%)		2/188 (1.1%)
Jugular vein thrombosis	0/101 (0%)		1/188 (0.5%)
Vena cava thrombosis	1/101 (1%)		0/188 (0%)
Venous thrombosis	2/101 (2%)		0/188 (0%)
Other (Not Including Serious) Adverse Events
	Cetuximab Plus FOLFIRI		Cetuximab Plus FOLFOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/101 (92.1%)		177/188 (94.1%)
Blood and lymphatic system disorders
Neutropenia	53/101 (52.5%)		100/188 (53.2%)
Leukopenia	24/101 (23.8%)		28/188 (14.9%)
Anaemia	14/101 (13.9%)		13/188 (6.9%)
Thrombocytopenia	6/101 (5.9%)		44/188 (23.4%)
Cardiac disorders
Cardiac disorders	10/101 (9.9%)		8/188 (4.3%)
Eye disorders
Eye disorders	9/101 (8.9%)		20/188 (10.6%)
Gastrointestinal disorders
Nausea	61/101 (60.4%)		68/188 (36.2%)
Diarrhoea	58/101 (57.4%)		79/188 (42%)
Vomiting	37/101 (36.6%)		63/188 (33.5%)
Stomatitis	31/101 (30.7%)		52/188 (27.7%)
Constipation	22/101 (21.8%)		42/188 (22.3%)
Abdominal pain	20/101 (19.8%)		14/188 (7.4%)
Mouth ulceration	10/101 (9.9%)		19/188 (10.1%)
Dyspepsia	10/101 (9.9%)		10/188 (5.3%)
Abdominal pain upper	6/101 (5.9%)		12/188 (6.4%)
Abdominal distension	6/101 (5.9%)		5/188 (2.7%)
Gastrooesophageal reflux disease	6/101 (5.9%)		5/188 (2.7%)
General disorders
Fatigue	21/101 (20.8%)		48/188 (25.5%)
Pyrexia	17/101 (16.8%)		34/188 (18.1%)
Mucosal inflammation	15/101 (14.9%)		54/188 (28.7%)
Asthenia	7/101 (6.9%)		14/188 (7.4%)
Hepatobiliary disorders
Hepatic function abnormal	6/101 (5.9%)		9/188 (4.8%)
Immune system disorders
Drug hypersensitivity	1/101 (1%)		17/188 (9%)
Infections and infestations
Paronychia	32/101 (31.7%)		48/188 (25.5%)
Upper respiratory tract infection	11/101 (10.9%)		14/188 (7.4%)
Conjunctivitis	5/101 (5%)		19/188 (10.1%)
Nasopharyngitis	1/101 (1%)		11/188 (5.9%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	9/101 (8.9%)		15/188 (8%)
Investigations
Weight decreased	9/101 (8.9%)		10/188 (5.3%)
Alanine aminotransferase increased	6/101 (5.9%)		14/188 (7.4%)
Aspartate aminotransferase increased	3/101 (3%)		14/188 (7.4%)
Platelet count decreased	0/101 (0%)		10/188 (5.3%)
Metabolism and nutrition disorders
Decreased appetite	33/101 (32.7%)		51/188 (27.1%)
Hypokalaemia	21/101 (20.8%)		29/188 (15.4%)
Hypocalcaemia	8/101 (7.9%)		7/188 (3.7%)
Hypomagnesaemia	7/101 (6.9%)		31/188 (16.5%)
Musculoskeletal and connective tissue disorders
Back pain	7/101 (6.9%)		8/188 (4.3%)
Nervous system disorders
Dizziness	9/101 (8.9%)		23/188 (12.2%)
Headache	6/101 (5.9%)		14/188 (7.4%)
Dysgeusia	6/101 (5.9%)		13/188 (6.9%)
Neuropathy peripheral	4/101 (4%)		63/188 (33.5%)
Hypoaesthesia	3/101 (3%)		14/188 (7.4%)
peripheral sensory neuropathy	1/101 (1%)		34/188 (18.1%)
Psychiatric disorders
Insomnia	13/101 (12.9%)		20/188 (10.6%)
Renal and urinary disorders
Renal and urinary disorders	7/101 (6.9%)		11/188 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	16/101 (15.8%)		23/188 (12.2%)
Dyspnoea	8/101 (7.9%)		15/188 (8%)
Hiccups	7/101 (6.9%)		6/188 (3.2%)
Epistaxis	2/101 (2%)		17/188 (9%)
Skin and subcutaneous tissue disorders
Rash	55/101 (54.5%)		115/188 (61.2%)
Alopecia	30/101 (29.7%)		17/188 (9%)
Dry skin	17/101 (16.8%)		29/188 (15.4%)
Pruritus	16/101 (15.8%)		24/188 (12.8%)
Acne	16/101 (15.8%)		22/188 (11.7%)
Dermatitis acneiform	12/101 (11.9%)		21/188 (11.2%)
Palmar-plantar erythrodysaesthesia syndrome	11/101 (10.9%)		30/188 (16%)
Skin fissures	11/101 (10.9%)		11/188 (5.9%)
Vascular disorders
Phlebitis	1/101 (1%)		11/188 (5.9%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.