Cetuximab Standard or Dose Escalation in First Line Color... | NCT01251536

ID	Type	Description	Link
2009-009992-36	EudraCT Number

Name	Class
Merck KGaA, Darmstadt, Germany	INDUSTRY

Label	Type	Description	Intervention Names
Arm B - standard dose of cetuximab	Other	Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab 250 mg/m2 weekly. No comparison between arms was planned.	Drug: Standard first line treatment with cetuximab + Folfiri
Arm A - dose escalation of cetuximab	Experimental	Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly.	Drug: Dose escalation of cetuximab

Name	Type	Description	Arm Group Labels	Other Names
Dose escalation of cetuximab	Drug	Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly

Measure	Description	Time Frame
PFS Probability Rate at 9 Months in the Dose Escalation Arm	A precise estimate (+/- 10%) of the probability of not having progression at 9 months. This measure is an estimation derived from the Kaplan-Meier algorithm and does not represent a dimple percentage of participants.	9 months

Measure	Description	Time Frame
Progression Free Survival (PFS) Median Time	Progression free survival time was considered from start of treatment until the first observation of disease progression or death from any cause, whichever occurred first. All patients (ITT).	Treatment + follow-up (3 years from database lock)
Progression Free Survival (PFS) Median Time for Resected Patients

Name	Affiliation	Role
Eric Van Cutsem, MD	UZ Leuven	Principal Investigator

ID	Title	Description
FG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly

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

PFS Probability Rate at 9 Months in the Dose Escalation Arm

A precise estimate (+/- 10%) of the probability of not having progression at 9 months. This measure is an estimation derived from the Kaplan-Meier algorithm and does not represent a dimple percentage of participants.

Posted

Number

percent probability

9 months

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.
OG002	Not Allocated	Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.
OG003	ITT / Safety Set	All patients for whom there was evidence they were administered any dose of cetuximab or FOLFIRI on study. For this study, the safety set includes all patients and is identical to the intention-to-treat (ITT) set.

Units	Counts
Participants	OG0008 OG00193 OG0027 OG003

Title

Denominators

Categories

Title	Measurements
	OG00045 OG00148 OG0020 OG003

Secondary

Progression Free Survival (PFS) Median Time

Progression free survival time was considered from start of treatment until the first observation of disease progression or death from any cause, whichever occurred first. All patients (ITT).

All patients for whom there was evidence they were administered any dose of cetuximab or FOLFIRI on study. For this study, the safety set includes all patients and is identical to the intention-to-treat (ITT) set.

Posted

Median

95% Confidence Interval

Months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Progression Free Survival (PFS) Median Time for Resected Patients

Progression free survival time was considered from start of treatment until the first observation of disease progression or death from any cause, whichever occurred first. This is the subset of resected patients (resection of secondary lesions with curative intent was performed). Patients resected after they started subsequent anti-cancer treatment or after progression on treatment were not considered as 'resected for metastatic lesions on study'. Patients were not censored at time of surgery.

Posted

Median

95% Confidence Interval

Months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)

Posted

Number

95% Confidence Interval

Hazard ratio

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Death Rates by 3 Years Follow-up

Deaths by 3 years follow-up after last cetuximab administration + 30 days. All patients (ITT).

Posted

Count of Participants

Participants

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Overall Survival (OS) Median Time

Overall survival was considered from start of treatment to death. All patients (ITT).

Posted

Median

95% Confidence Interval

months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Overall Survival (OS) Median Time for Resected Patients

Overall survival was considered from start of treatment to death. Subset of resected patients (resection of secondary lesions with curative intent was performed). Patients resected after they started subsequent anti-cancer treatment (600-01-006 and 600-04-006) or after progression (100-02-002,

End point description:

Clinical trial results 2009-009992-36 version 1 EU-CTR publication date: Page 15 of 38 200-03-001, and 600-01-038) were not considered as 'resected for metastatic lesions on study.

Posted

Median

95% Confidence Interval

Months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Overall Response

Overall response is defined as the best tumor response on treatment of either complete response (CR) or partial response (PR) (CR + PR). Tumor response is based on the CT/MRI assessments of target and non-target lesions as well as considering the occurrence of new lesions as per RECIST criteria. All patients (ITT).

Posted

Count of Participants

Participants

Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Overall Response in Patients With Liver-limited Disease

Overall response is defined as the best tumor response on treatment of either complete response (CR) or partial response (PR) (CR + PR). Tumor response is based on the imaging (CT/MRI) assessments of target and non-target lesions as well as considering the occurrence of new lesions as per RECIST criteria. Subset of patients with liver-limited disease.

Posted

Count of Participants

Participants

Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Disease Control

Disease control is defined as a best response on treatment (e.g. till end of treatment evaluation) of either complete response (CR), partial response (PR), or stable disease (SD) (CR + PR + SD). RECIST criteria (CT/MRI). All patients (ITT).

Posted

Count of Participants

Participants

Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Disease Control in Patients With Liver-limited Disease

Posted

Count of Participants

Participants

Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Duration of Response

The duration of response in responding patients is defined as the time interval from the time measurement criteria are first met for CR/PR during treatment to either the first time disease progression is documented or death. Subset of responders.

Posted

Median

95% Confidence Interval

Months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Duration of Response in Liver-limited Disease Patients

Posted

Median

95% Confidence Interval

Months

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Resections for Metastatic Lesions

All patients were deemed non-resectable at baseline but some became resectable during or posttreatment.

All patients (ITT). Only those patients in whom resection of secondary lesions with curative intent was performed were considered as 'resected'. Patients resected after they started subsequent anti-cancer treatment (600-01-006 and 600-04-006) or after progression (100-02-002, 200-03-001, and 600-01-038) were not considered as 'resected for metastatic lesions on study'.

Posted

Count of Participants

Participants

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

R0 Rate (Free of Tumor After Resection for Metastatic Lesions)

Rate of patients free of tumor after surgery. Subset of resected patients (resection of secondary lesions with curative intent was performed). Patients resected after they started subsequent anti-cancer treatment (600-01-006 and 600-04-006) or after progression (100-02-002, 200-03-001, and 600-01- 038) were not considered as 'resected for metastatic lesions on study'.

Posted

Count of Participants

Participants

Treatment + follow-up (3 years from database lock)

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Skin Toxicity (Safety)

Treatment-emergent adverse events identified by the investigator as skin reaction or events with description skin infection or nail infection. Grading of severity was per NCI CTCAE version 4.0. All events are summarized based on the timing of occurrence per Arm in the first two rows, and worst grade per patient events are presented (following 3 rows). Grade 0 is the absence of any skin reaction and grade 3 is worst severity. All patients treated (Safety set).

Note: There were 3 deviations from arm allocation rules based on the occurrence of skin toxicity. Detailed data is available upon request.

Posted

Number

participants

From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Laboratory Safety Assessments

Severe laboratory abnormalities (hematology and biochemistry grade 3 and higher). Worst grade per patient. All patients treated (Safety set).

Posted

Number

participants

From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Secondary

Deaths Till 30 Days From Last Cetuximab Administration

Deaths of all causes occuring between the signature of consent and the date of last cetuximab administration + 30 days are listed per arm. None of these fatalities were deemed related to the investigational drug.

Posted

Number

participants

From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.

ID	Title	Description
OG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
OG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Circulatory failure	Vascular disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Thromoembolic event	Vascular disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Anaphylaxis	Immune system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
General deterioration	General disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0015 events3 affected93 at risk EG0020 events0 affected7 at risk
Fatigue	General disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Ventricullar fibrillation	Cardiac disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Cardiac arrest	Cardiac disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0015 events3 affected93 at risk EG0020 events0 affected7 at risk
Anemia	Blood and lymphatic system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Leukocytosis	Blood and lymphatic system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Febrile neutropenia	Blood and lymphatic system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected7 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Respiratory insufficiency	Respiratory, thoracic and mediastinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Peripheral sensory neuropathy	Nervous system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Syncope	Nervous system disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected7 at risk
Abdominal pain	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected7 at risk
Colonic haemorrhage	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hemorrhoids	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Colonic obstruction	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0014 events3 affected93 at risk EG0020 events0 affected7 at risk
Diarrhea	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0002 events2 affected8 at risk EG00120 events14 affected93 at risk EG0020 events0 affected7 at risk
Ileus	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Colonic perforation	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected7 at risk
Jejunal obstruction	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Small intestinal obstruction	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0021 events1 affected7 at risk
Mucositis oral	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0013 events3 affected93 at risk EG0020 events0 affected7 at risk
Vomiting	Gastrointestinal disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Hepatic hematoma	Hepatobiliary disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Gallbladder obstruction	Hepatobiliary disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected7 at risk
Hepatic pain	Hepatobiliary disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Portal vein thrombosis	Hepatobiliary disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Acute kidney injury	Renal and urinary disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hypertrichosis	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Fissure/feet	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Fissure/fingers	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Pruritus	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0013 events2 affected93 at risk EG0020 events0 affected7 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected7 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG00125 events17 affected93 at risk EG0020 events0 affected7 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Anorexia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0013 events2 affected93 at risk EG0020 events0 affected7 at risk
Diabetes angiopathy	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hypokalemia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0004 events2 affected8 at risk EG0017 events2 affected93 at risk EG0020 events0 affected7 at risk
Dehydration	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hyperglycemia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hypophosphatemia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected7 at risk
Hyponatremia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0002 events1 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Hypomagnesemia	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected7 at risk
Severe undernutrition	Metabolism and nutrition disorders	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Bronchial infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected7 at risk
Enterocolitis infectious	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Acute cytolysis due to viral infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Erysipelas	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Lung infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0013 events3 affected93 at risk EG0020 events0 affected7 at risk
Paronychia	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0013 events1 affected93 at risk EG0020 events0 affected7 at risk
Catheter related infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0020 events0 affected7 at risk
Kidney infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Papulopustular rash	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG00116 events7 affected93 at risk EG0020 events0 affected7 at risk
Skin infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Pelvic infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Peritoneal infection	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected7 at risk
Yersinia enterocolitica gastroenteritis	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 at risk
Sepsis	Infections and infestations	NCI CTCAE V4.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected7 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

ID	Title	Description
BG000	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly
BG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.
BG002	Not Allocated	Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.
BG003	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	Arm A - Dose Escalation of Cetuximab	Patients with no cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were increased at day 22. Dose escalation of cetuximab: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly	1	8	6	8	6	8
EG001	Arm B - Standard Dose of Cetuximab	Patients with any grade cetuximab-related skin toxicity or other significant toxicity after first 3 weeks of treatment with cetuximab standard dosing in combination with FOLFIRI, in whom cetuximab doses were maintained at standard levels at day 22. Standard first line treatment with cetuximab + Folfiri: Dose, frequency & treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.	6	93	39	93	66	93
EG002	Not Allocated	Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	2	7	6	7	3	7