Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plu... | NCT00439517

Label	Type	Description	Intervention Names
1	Experimental	UFOX + Cetuximab	Drug: UFOX + Cetuximab
2	Active Comparator	FOLFOX4 + Cetuximab	Drug: FOLFOX4 + Cetuximab

Name	Type	Description	Arm Group Labels	Other Names
UFOX + Cetuximab	Drug	Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21

Measure	Description	Time Frame
Progression-free Survival (PFS)	Duration from randomization until progression or death due to any cause. Only deaths within 12 weeks of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment. Response and progression were assessed by the Investigators using response evaluation criteria in solid tumors (RECIST) 1.0 criteria	Time from randomization to disease progression, death, or last tumor assessment reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009

Measure	Description	Time Frame
Best Overall Response (BOR)	BOR defined as percentage of subjects, whose BOR was either (confirmed) complete response (CR) or partial response (PR), relative to the number of subjects belonging to the study population of interest. CR defined as "Disappearance of all target lesions plus disappearance of all non-target lesions & without appearance of any new lesions; confirmed minimum 4 weeks later. PR defined as "At least 30% reduction in the SOLD of target lesions plus no significant change in non-target lesions to qualify for either CR or PD without appearance of new lesions; confirmed minimum 4 weeks later

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Signed written informed consent
Inpatient or outpatient ≥ 18 years of age
Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
First occurrence of metastatic disease (not curatively resectable)
Presence of at least one lesion measurable uni dimensionally by computerised tomography (CT) scan or magnetic resonance imaging (MRI). (Target lesion(s) must not lie within an irradiated area)
Life expectancy of ≥ 3 months
Karnofsky performance status of ≥ 60, at study entry
White blood cell count (WBC) ≥ 3 x 10^9/L, with neutrophils ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 9 g/dL
Aspartate transaminase and alanine transaminase ≤ 2.5 x Upper Limit of Normal (ULN) (≤ 5 x ULN if liver metastasis are present)
Normal serum creatinine (in case of elevated creatinine, labelled ethylenediaminetetraacetic acid clearance ≥ 65 mL/min is acceptable)
Effective contraception for both male and female subjects if the risk of conception exists
Tumor biopsy or archived sample available

Exclusion criteria:

Brain metastasis and/or leptomeningeal disease (known or suspected)
Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment.
Previous oxaliplatin-based chemotherapy
Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to randomization
Concurrent or previous chronic systemic immune therapy, targeted therapy, anti-vascular epithelial growth factor (VEGF) therapy, epidermal growth factor receptor (EGFR) pathway targeting therapy not indicated in the study protocol
Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception
Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
Peripheral neuropathy >grade 1
Known hypersensitivity reaction to any of the components of the treatment.
Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive cancer of the cervix. (Subjects with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the study)
Pregnancy (absence to be confirmed by ß-human chorionic gonadotrophin test) or lactation period
Known drug abuse/alcohol abuse
Legal incapacity or limited legal capacity
Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent
Participation in another clinical study within the 30 days before randomization
Significant disease which, in the investigator's opinion, would exclude the subject from the study

Name	Affiliation	Role
Jean-Yves Douillard, MD PhD	Centre R Gauducheau	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Buenos Aires			Argentina
Research Site

PubMed Identifier	Type	Citation	Retractions
24370353	Result	Douillard JY, Zemelka T, Fountzilas G, Barone C, Schlichting M, Heighway J, Eggleton SP, Srimuninnimit V. FOLFOX4 with cetuximab vs. UFOX with cetuximab as first-line therapy in metastatic colorectal cancer: The randomized phase II FUTURE study. Clin Colorectal Cancer. 2014 Mar;13(1):14-26.e1. doi: 10.1016/j.clcc.2013.11.009. Epub 2013 Nov 16.

ID	Title	Description
FG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21

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)

Duration from randomization until progression or death due to any cause. Only deaths within 12 weeks of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment. Response and progression were assessed by the Investigators using response evaluation criteria in solid tumors (RECIST) 1.0 criteria

Intention-to-treat (ITT) population i.e. all randomized subjects .

Posted

Median

95% Confidence Interval

months

Time from randomization to disease progression, death, or last tumor assessment reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Units	Counts
Participants	OG000152 OG001150

Title

Denominators

Categories

Title	Measurements
	OG0006.6(5.6 to 7.2) OG0018.2(7.5 to 9.2)

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		Stratified log rank	Kaplan-Meier method was used to estimate median PFS time. HR was calculated using Cox proportional hazards model stratified by randomization strata.	0.0048		Hazard Ratio (HR)	0.677			2-Sided	95	0.515	0.889				No	Superiority or Other

Secondary

Best Overall Response (BOR)

BOR defined as percentage of subjects, whose BOR was either (confirmed) complete response (CR) or partial response (PR), relative to the number of subjects belonging to the study population of interest. CR defined as "Disappearance of all target lesions plus disappearance of all non-target lesions & without appearance of any new lesions; confirmed minimum 4 weeks later. PR defined as "At least 30% reduction in the SOLD of target lesions plus no significant change in non-target lesions to qualify for either CR or PD without appearance of new lesions; confirmed minimum 4 weeks later

ITT population i.e. all randomized subjects.

Posted

Number

95% Confidence Interval

percentage of participants

Evaluations were performed every 8 weeks until disease progression, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Secondary

Overall Survival (OS)

Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

ITT population i.e. all randomized subjects.

Posted

Median

95% Confidence Interval

months

Time from randomization to death or last known to be alive, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Secondary

Overall Survival (OS)

Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

ITT population i.e. all randomized subjects.

Posted

Median

95% Confidence Interval

months

Time from randomization to death or last known to be alive, reported between day of first patient randomised, Feb 2007, until cut off date, 31 Aug 2011

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Secondary

Quality of Life (QOL) Functional Assessment of Cancer Therapy-Colorectal (FACT-C)

All of the single-item measures of the FACT-C are assessed on ordinal response categories ranging from 0="Not at all" to 4="Very much". For scoring purposes the response scores are reversed on negatively phrased questions. The principle for scoring the sub-scales is the same in all cases: subscale score = (Sum of items × Number of items in the subscale) / numbers of items answered. The lowest possible total score is 0 and the highest is 136. A high scale score represents a high QOL.

Patients were considered evaluable for FACT-C provided they had at least one evaluable FACT-C questionnaire and provided that they were also included in the ITT Population

Posted

Least Squares Mean

Standard Error

scores on a scale

At baseline, at every first day of every third cycle during active - treatment, and at final tumor assessment , reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009. Cycles were 4 weeks long unless dosing delays

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001

Secondary

QOL EuroQuol-5D (EQ-5D) Health Outcome Questionnaire

The EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QOL.

Patients were considered evaluable for EQ-5D provided they had at least one evaluable EQ-5D questionnaire and provided that they were also included in the ITT Population.

Posted

Least Squares Mean

Standard Error

scores on a scale

at baseline, at every first day of every third cycle during active - treatment, and at final tumor assessment , reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009. All cycles were 4 weeks long unless dosing delays

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21

Secondary

QOL Therapy Preference Questionnaire (TPQ)

TPQ was used to investigate which features of chemotherapy treatment are the most relevant in ensuring patient satisfaction. The most essential characteristics of a cancer medication are shown at baseline and at cycle 3, along with percentage of subjects selecting that characteristic.

Patients were considered evaluable for TPQ provided they had at least one evaluable TPQ questionnaire and they were also included in the ITT TPQ subset population.

The most essential characteristics of a cancer medication score are shown at baseline and cycle 3, no further cycles are available due to the low number of patients in later cycles

Posted

Number

percentage of participants

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab

Secondary

Treatment Impact on Social Daily Living and Health Care Resource Utilization

Non-protocol medical care visits and consultations

ITT population

Posted

Number

visits or consultations

From randomisation until final visit, reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Secondary

Safety - Number of Patients Experiencing Any Adverse Event

Please refer to Adverse Events section for details of individual serious adverse events and other adverse events

Safety population

Posted

Number

participants

Time from first dose up to 30 days after last dose of study treatment, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009

ID	Title	Description
OG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
OG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0011 affected150 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Splenic vein thrombosis	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Cardiac failure	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Myocardial infarction	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Ulcerative keratitis	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0014 affected150 at risk
Anal fistula	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Colitis	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00013 affected151 at risk EG0014 affected150 at risk
Faecaloma	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Ileus	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0012 affected150 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0012 affected150 at risk
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0004 affected151 at risk EG0010 affected150 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Subileus	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Vomiting	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG0013 affected150 at risk
Asthenia	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Chills	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0012 affected150 at risk
General physical health deterioration	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0014 affected150 at risk
Inflammation	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Pyrexia	General disorders	MedDRA (12.0)	Systematic Assessment	EG0003 affected151 at risk EG0018 affected150 at risk
Biliary colic	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Hepatorenal syndrome	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Anal abscess	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Catheter related infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Cellulitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Central line infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0015 affected150 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Hepatitis C	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Pneumonia	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0011 affected150 at risk
Pyelonephritis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Rectal abscess	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Septic shock	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0012 affected150 at risk
Urinary tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Urosepsis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0012 affected150 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Blood glucose abnormal	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0011 affected150 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0002 affected151 at risk EG0011 affected150 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0002 affected151 at risk EG0010 affected150 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Coma hepatic	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Grand mal convulsion	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Syncope	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Anxiety	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Confusional state	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Ureteric perforation	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Urethral disorder	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Urinary bladder haemorrhage	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Urinary retention	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Vaginal fistula	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0012 affected150 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0012 affected150 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0012 affected150 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk
Arterial thrombosis	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Circulatory collapse	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected151 at risk EG0011 affected150 at risk
Femoral artery embolism	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected151 at risk EG0010 affected150 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG00165 affected150 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG00033 affected151 at risk EG00137 affected150 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG00128 affected150 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG00015 affected151 at risk EG00126 affected150 at risk
Conjunctivitis	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG00014 affected151 at risk EG00114 affected150 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00079 affected151 at risk EG00172 affected150 at risk
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00067 affected151 at risk EG00155 affected150 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00015 affected151 at risk EG00136 affected150 at risk
Vomiting	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00040 affected151 at risk EG00132 affected150 at risk
Constipation	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00029 affected151 at risk EG00130 affected150 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00034 affected151 at risk EG00125 affected150 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG0018 affected150 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG0018 affected150 at risk
Flatulence	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG0011 affected150 at risk
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG00038 affected151 at risk EG00138 affected150 at risk
Pyrexia	General disorders	MedDRA (12.0)	Systematic Assessment	EG00030 affected151 at risk EG00136 affected150 at risk
Mucosal inflammation	General disorders	MedDRA (12.0)	Systematic Assessment	EG00015 affected151 at risk EG00134 affected150 at risk
Asthenia	General disorders	MedDRA (12.0)	Systematic Assessment	EG00025 affected151 at risk EG00127 affected150 at risk
Oedema peripheral	General disorders	MedDRA (12.0)	Systematic Assessment	EG00011 affected151 at risk EG00111 affected150 at risk
Chills	General disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0019 affected150 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG00012 affected151 at risk EG0016 affected150 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (12.0)	Systematic Assessment	EG00012 affected151 at risk EG00110 affected150 at risk
Hypersensitivity	Immune system disorders	MedDRA (12.0)	Systematic Assessment	EG0003 affected151 at risk EG0018 affected150 at risk
Paronychia	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG00026 affected151 at risk EG00133 affected150 at risk
Folliculitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0008 affected151 at risk EG00114 affected150 at risk
Nasopharyngitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0006 affected151 at risk EG00111 affected150 at risk
Pharyngitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0008 affected151 at risk EG0017 affected150 at risk
Weight decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG00012 affected151 at risk EG00116 affected150 at risk
Alanine aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG0018 affected150 at risk
Platelet count decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG0016 affected150 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG0015 affected150 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG00040 affected151 at risk EG00136 affected150 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG00017 affected151 at risk EG00115 affected150 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG00015 affected151 at risk EG00114 affected150 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG00110 affected150 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0018 affected150 at risk
Paraesthesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00038 affected151 at risk EG00143 affected150 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00029 affected151 at risk EG00127 affected150 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00017 affected151 at risk EG00122 affected150 at risk
Dysgeusia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00013 affected151 at risk EG00120 affected150 at risk
Polyneuropathy	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0006 affected151 at risk EG00117 affected150 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0006 affected151 at risk EG00110 affected150 at risk
Dysaesthesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00011 affected151 at risk EG0015 affected150 at risk
Insomnia	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG0015 affected150 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0009 affected151 at risk EG00113 affected150 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0018 affected150 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0008 affected151 at risk EG0017 affected150 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00063 affected151 at risk EG00147 affected150 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00040 affected151 at risk EG00145 affected150 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00027 affected151 at risk EG00129 affected150 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00013 affected151 at risk EG00122 affected150 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0008 affected151 at risk EG00115 affected150 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00020 affected151 at risk EG00114 affected150 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG00113 affected150 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0006 affected151 at risk EG00113 affected150 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG00010 affected151 at risk EG00112 affected150 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0007 affected151 at risk EG00111 affected150 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0005 affected151 at risk EG0019 affected150 at risk
Hypertension	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0008 affected151 at risk EG00111 affected150 at risk

ID	Term
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

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

ID	Title	Description
BG000	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21
BG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16
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	UFOX + Cetuximab	UFOX is a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks) Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21 Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21			52	151	151	151
EG001	FOLFOX4 + Cetuximab	FOLFOX4 is a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid. Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22) Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks) 5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16 Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16			48	150	146	150