A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-F... | NCT01228734

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cetuximab + FOLFOX-4	Experimental	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	Drug: Cetuximab Drug: Oxaliplatin Drug: Folinic Acid Drug: 5Fluorouracil
FOLFOX-4	Active Comparator	Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	Drug: Oxaliplatin Drug: Folinic Acid Drug: 5Fluorouracil

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cetuximab	Drug	Cetuximab was administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity to cetuximab.

Measure	Description	Time Frame
Progression Free Survival (PFS) Time	PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.	Baseline up to 333 weeks

Measure	Description	Time Frame
Overall Survival (OS) Time	OS was defined as the time (in months) from randomization to death. For subjects who were still alive at the analysis data cut-off date or who lost to follow-up, survival was censored at the last recorded date that the subject was known to be alive.	Baseline up to 333 weeks
Best Overall Response Rate (ORR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed written informed consent (first and second)
Chinese with Chinese citizenship
Male or female subjects greater than or equal to (>=) 18 years of age
Medically accepted effective contraception if procreative potential exists (applicable for both male and female subjects until at least 90 days after the last dose of trial treatment)
Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
First occurrence of metastatic disease (not curatively resectable) RAS wild-type status in tumor tissue
At least one measurable lesion by computer tomography (CT) or magnetic resonance imaging (MRI) according to RECIST (not in an irradiated area)
Life expectancy of at least 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry
White blood cell count >= 3 × 10x9/L with neutrophils >= 1.5 × 10x9/L, platelet count >= 100 × 10x9/L and hemoglobin >= 6.21 mmol/L (10 g/dL)
Total bilirubin <= 1.5 × upper limit of reference range
Aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 × upper limit of reference range or <= 5 × upper reference range in subjects with liver metastasis
Serum creatinine <= 1.5 × upper limit of reference range
Recovery from relevant toxicity due to previous treatment before trial entry

Exclusion Criteria:

Previous chemotherapy for CRC except adjuvant treatment if terminated > 9 months (oxaliplatin-based chemotherapy) or > 6 months (non-oxaliplatin-based chemotherapy) before the start of treatment in this trial
Radiotherapy or surgery (excluding prior diagnostic biopsy) in the 30 days before trial treatment
Previous treatment with monoclonal antibody therapy, vascular endothelial growth factor (VEGF) pathway-targeting therapy, epidermal growth factor receptor (EGFR) pathway-targeting therapy, or other signal transduction inhibitors
History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation
Renal replacement therapy
Intake of any investigational medication within 30 days before trial entry
Concurrent chronic systemic immune therapy or hormone therapy except physiologic replacement
Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) within 3 weeks of trial entry (these growth factors may be used during the trial thereafter)
Other non-permitted concomitant anticancer therapies
Known brain metastasis and/or leptomeningeal disease. Subjects with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 5 years, or left ventricular ejection fraction below the institutional range of normal on a baseline multiple gated acquisition scan or echocardiogram
Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0), including active tuberculosis
Known and declared history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
Peripheral neuropathy > grade 1
Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, or liver failure
Known hypersensitivity or allergic reactions against any of the components of the trial treatments
Pregnancy (absence to be confirmed by serum β-human chorionic gonadotropin test) or breastfeeding
Ongoing alcohol or drug abuse
Presence of a medical or psychological condition that would not permit the subject to complete the trial or sign informed consent
Participation in another clinical trial within the past 30 days
Other significant disease that in the investigator's opinion should exclude the subject from the trial
Legal incapacity or limited legal capacity

Name	Affiliation	Role
Medical Responsible	Merck Serono Co., Ltd., Beijing, an affiliate of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Fujian Province Cancer Hospital		Fuzhou	Fujian	350014	China
Fuzhou General Hospital

PubMed Identifier	Type	Citation	Retractions
32051297	Derived	Wang H, Huang L, Gao P, Zhu Z, Ye W, Ding H, Fang L. Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial. BMJ Open. 2020 Feb 12;10(2):e030738. doi: 10.1136/bmjopen-2019-030738.
31849531	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cetuximab + FOLFOX4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival (PFS) Time

PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to 333 weeks

ID	Title	Description
OG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
OG001	FOLFOX-4	Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Units	Counts
Participants	OG000193 OG001200

Title

Denominators

Categories

Title	Measurements
	OG0009.2(8.8 to 10.9) OG0017.4(5.8 to 7.5)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		<0.001		Hazard Ratio (HR)	0.629			2-Sided	95	0.498	0.794					Superiority or Other (legacy)

Secondary

Overall Survival (OS) Time

OS was defined as the time (in months) from randomization to death. For subjects who were still alive at the analysis data cut-off date or who lost to follow-up, survival was censored at the last recorded date that the subject was known to be alive.

MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to 333 weeks

ID	Title	Description
OG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
OG001	FOLFOX-4

Secondary

Best Overall Response Rate (ORR)

The Best ORR was defined as the percentage of subjects having achieved complete response (CR) or partial response (PR) according to RECIST version 1.0 as determined by the IRC. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions.

MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

Posted

Number

95% Confidence Interval

percentage of subjects

Baseline up to 333 weeks

ID	Title	Description
OG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Secondary

Time to Treatment Failure (TTF)

TTF was defined as time from randomization to date of the first occurrence of radiologically confirmed PD as determined by IRC, Clinical PD according to the Investigator's assessment (if radiological confirmation of PD by IRC was unavailable), discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death within 90 days of last tumor assessment or randomization. Subjects without event were censored on the date of last tumor assessment.

MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to 333 weeks

ID	Title	Description
OG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Secondary

Number of Subjects With Curative Surgery of Liver Metastases

The number of subjects who underwent liver metastatic surgery after start of treatment and the outcome of surgery with respect to residual tumor after surgery (R0, R1, R2, not evaluable) were summarized. In case of resection of more than one metastasis, the worst outcome of surgery defined the overall status of a subject. R0 = No residual tumor after resection (all lesions resected completely); R1 = Metastases not resected completely with microscopic residual lesions; and R2 = Metastases not resected completely with macroscopic residual lesions.

MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized. Here "Number Analyzed" signifies those subjects who were evaluable for the specified categories.

Posted

Number

subjects

Baseline up to 333 weeks

ID	Title	Description
OG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
BONE MARROW FAILURE	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0012 affected199 at risk
THROMBOCYTOPENIC PURPURA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0012 affected199 at risk
ATRIAL FLUTTER	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
VENTRICULAR TACHYCARDIA	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
RETINAL DETACHMENT	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
ANAL FISTULA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
ENTERITIS	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
INCARCERATED INGUINAL HERNIA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected194 at risk EG0014 affected199 at risk
INTESTINAL PERFORATION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
LARGE INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
SMALL INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
MULTI-ORGAN FAILURE	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected194 at risk EG0013 affected199 at risk
PYREXIA	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
SUDDEN DEATH	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
HEPATIC FAILURE	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected194 at risk EG0010 affected199 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
JAUNDICE CHOLESTATIC	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
DRUG HYPERSENSITIVITY	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected194 at risk EG0011 affected199 at risk
ANAL ABSCESS	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
EPIDIDYMITIS	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
PNEUMONIA	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
SKIN INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
STAPHYLOCOCCAL BACTERAEMIA	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
STAPHYLOCOCCAL INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
HAEMOGLOBIN DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
TYPE 2 DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
CEREBRAL INFARCTION	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0012 affected199 at risk
HEADACHE	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
HEPATIC ENCEPHALOPATHY	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
SYNCOPE	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
SUICIDE ATTEMPT	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
RENAL FAILURE	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
URETERIC OBSTRUCTION	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected194 at risk EG0010 affected199 at risk
DYSPNOEA AT REST	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected194 at risk EG0010 affected199 at risk
AXILLARY VEIN THROMBOSIS	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
JUGULAR VEIN THROMBOSIS	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
PHLEBITIS	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0012 affected199 at risk
SUBCLAVIAN VEIN THROMBOSIS	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
VENOUS THROMBOSIS LIMB	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected194 at risk EG0011 affected199 at risk
THROMBOCYTOPENIC PURPURA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected194 at risk EG0011 affected199 at risk
LARGE INTESTINE POLYP	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
INFUSION SITE INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0011 affected199 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk
COLON CANCER METASTATIC	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0001 affected194 at risk EG0010 affected199 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG00028 affected194 at risk EG00124 affected199 at risk
BONE MARROW FAILURE	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG00018 affected194 at risk EG00114 affected199 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG000151 affected194 at risk EG001146 affected199 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG000156 affected194 at risk EG001149 affected199 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG00092 affected194 at risk EG001102 affected199 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00021 affected194 at risk EG00113 affected199 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00037 affected194 at risk EG00119 affected199 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00043 affected194 at risk EG00129 affected199 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00069 affected194 at risk EG00135 affected199 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00012 affected194 at risk EG0015 affected199 at risk
HAEMATOCHEZIA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected194 at risk EG0015 affected199 at risk
MOUTH ULCERATION	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00022 affected194 at risk EG0019 affected199 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00070 affected194 at risk EG00192 affected199 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00032 affected194 at risk EG00114 affected199 at risk
VOMITING	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00043 affected194 at risk EG00152 affected199 at risk
FATIGUE	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00077 affected194 at risk EG00156 affected199 at risk
PYREXIA	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00059 affected194 at risk EG00148 affected199 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG00019 affected194 at risk EG00121 affected199 at risk
LIVER INJURY	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG00012 affected194 at risk EG0016 affected199 at risk
DRUG HYPERSENSITIVITY	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG00018 affected194 at risk EG00115 affected199 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00010 affected194 at risk EG0014 affected199 at risk
PARONYCHIA	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00028 affected194 at risk EG0010 affected199 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00018 affected194 at risk EG00114 affected199 at risk
INFUSION RELATED REACTION	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG00020 affected194 at risk EG00112 affected199 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00065 affected194 at risk EG00154 affected199 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00058 affected194 at risk EG00158 affected199 at risk
BLOOD ALBUMIN DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00012 affected194 at risk EG0014 affected199 at risk
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00016 affected194 at risk EG0018 affected199 at risk
BLOOD BILIRUBIN INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00015 affected194 at risk EG0017 affected199 at risk
BLOOD LACTATE DEHYDROGENASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG00111 affected199 at risk
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00012 affected194 at risk EG00111 affected199 at risk
HAEMOGLOBIN DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00028 affected194 at risk EG00142 affected199 at risk
NEUTROPHIL COUNT DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG00113 affected199 at risk
PLATELET COUNT DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00019 affected194 at risk EG00118 affected199 at risk
WEIGHT DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00051 affected194 at risk EG00126 affected199 at risk
WEIGHT INCREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00023 affected194 at risk EG00114 affected199 at risk
WHITE BLOOD CELL COUNT DECREASED	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00014 affected194 at risk EG0019 affected199 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00075 affected194 at risk EG00160 affected199 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected194 at risk EG0015 affected199 at risk
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00013 affected194 at risk EG00113 affected199 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00023 affected194 at risk EG00114 affected199 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00016 affected194 at risk EG00118 affected199 at risk
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00012 affected194 at risk EG0014 affected199 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG00111 affected199 at risk
HYPOAESTHESIA	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG00025 affected194 at risk EG00127 affected199 at risk
NEUROTOXICITY	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG00015 affected194 at risk EG00118 affected199 at risk
INSOMNIA	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG00110 affected199 at risk
INSOMNIA	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected194 at risk EG00110 affected199 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00018 affected194 at risk EG00116 affected199 at risk
DERMATITIS ACNEIFORM	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00031 affected194 at risk EG0011 affected199 at risk
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00017 affected194 at risk EG0017 affected199 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected194 at risk EG0013 affected199 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG000120 affected194 at risk EG0017 affected199 at risk
SKIN FISSURES	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00017 affected194 at risk EG0010 affected199 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00065 affected194 at risk EG00138 affected199 at risk
HYPOMAGNESAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG00039 affected194 at risk EG0016 affected199 at risk
ASTHENIA	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG00113 affected199 at risk
HYPOPROTEINAEMIA	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected194 at risk EG00111 affected199 at risk
DRY SKIN	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected194 at risk EG0010 affected199 at risk

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D056831	Coordination Complexes
D009930	Organic Chemicals
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
BG001	FOLFOX-4	Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cetuximab + FOLFOX-4	Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	157	194	42	194	194	194
EG001	FOLFOX-4	Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	173	199	27	199	194	199

ID	Term
D000068818	Cetuximab
D000077150	Oxaliplatin
D002955	Leucovorin
D005472	Fluorouracil