Trial Outcomes & Findings for Cetuximab Standard or Dose Escalation in First Line Colorectal Cancer (NCT NCT01251536)

Last Updated: 2019-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

9 months

Results posted on

2019-10-11

Participant Flow

Participant milestones

Participant milestones
Measure	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	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.	Not Allocated Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.
Overall Study STARTED	8	93	7
Overall Study COMPLETED	8	93	7
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	Total n=108 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=8 Participants	0 Participants n=93 Participants	0 Participants n=7 Participants	0 Participants n=108 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=8 Participants	69 Participants n=93 Participants	5 Participants n=7 Participants	76 Participants n=108 Participants
Age, Categorical >=65 years	6 Participants n=8 Participants	24 Participants n=93 Participants	2 Participants n=7 Participants	32 Participants n=108 Participants
Age, Continuous	66 years n=8 Participants	60 years n=93 Participants	64 years n=7 Participants	60 years n=108 Participants
Sex: Female, Male Female	5 Participants n=8 Participants	24 Participants n=93 Participants	1 Participants n=7 Participants	30 Participants n=108 Participants
Sex: Female, Male Male	3 Participants n=8 Participants	69 Participants n=93 Participants	6 Participants n=7 Participants	78 Participants n=108 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Austria	0 participants n=8 Participants	4 participants n=93 Participants	0 participants n=7 Participants	4 participants n=108 Participants
Region of Enrollment Belgium	6 participants n=8 Participants	18 participants n=93 Participants	0 participants n=7 Participants	24 participants n=108 Participants
Region of Enrollment Hungary	0 participants n=8 Participants	20 participants n=93 Participants	2 participants n=7 Participants	22 participants n=108 Participants
Region of Enrollment France	0 participants n=8 Participants	5 participants n=93 Participants	2 participants n=7 Participants	7 participants n=108 Participants
Region of Enrollment Spain	2 participants n=8 Participants	46 participants n=93 Participants	3 participants n=7 Participants	51 participants n=108 Participants
Primary tumour Colon right	2 Participants n=8 Participants	16 Participants n=93 Participants	0 Participants n=7 Participants	18 Participants n=108 Participants
Primary tumour Colon left	2 Participants n=8 Participants	47 Participants n=93 Participants	5 Participants n=7 Participants	54 Participants n=108 Participants
Primary tumour Rectum	4 Participants n=8 Participants	30 Participants n=93 Participants	2 Participants n=7 Participants	36 Participants n=108 Participants
Tumour stage T1	0 Participants n=8 Participants	2 Participants n=93 Participants	0 Participants n=7 Participants	2 Participants n=108 Participants
Tumour stage T2	0 Participants n=8 Participants	2 Participants n=93 Participants	0 Participants n=7 Participants	2 Participants n=108 Participants
Tumour stage T3	2 Participants n=8 Participants	46 Participants n=93 Participants	2 Participants n=7 Participants	50 Participants n=108 Participants
Tumour stage T4	4 Participants n=8 Participants	27 Participants n=93 Participants	4 Participants n=7 Participants	35 Participants n=108 Participants
Tumour stage Tx	2 Participants n=8 Participants	16 Participants n=93 Participants	1 Participants n=7 Participants	19 Participants n=108 Participants
Nodal stage N0	2 Participants n=8 Participants	7 Participants n=93 Participants	2 Participants n=7 Participants	11 Participants n=108 Participants
Nodal stage N1	0 Participants n=8 Participants	24 Participants n=93 Participants	0 Participants n=7 Participants	24 Participants n=108 Participants
Nodal stage N2	3 Participants n=8 Participants	34 Participants n=93 Participants	2 Participants n=7 Participants	39 Participants n=108 Participants
Nodal stage Nx	3 Participants n=8 Participants	28 Participants n=93 Participants	3 Participants n=7 Participants	34 Participants n=108 Participants
ECOG PS PS = 0	6 Participants n=8 Participants	48 Participants n=93 Participants	1 Participants n=7 Participants	55 Participants n=108 Participants
ECOG PS PS = 1	2 Participants n=8 Participants	45 Participants n=93 Participants	6 Participants n=7 Participants	53 Participants n=108 Participants
Metastases Liver only	4 Participants n=8 Participants	39 Participants n=93 Participants	2 Participants n=7 Participants	45 Participants n=108 Participants
Metastases Liver + other	4 Participants n=8 Participants	45 Participants n=93 Participants	2 Participants n=7 Participants	51 Participants n=108 Participants
Metastases Other (no liver)	0 Participants n=8 Participants	9 Participants n=93 Participants	3 Participants n=7 Participants	12 Participants n=108 Participants
Index lesions 1 location	4 Participants n=8 Participants	44 Participants n=93 Participants	4 Participants n=7 Participants	52 Participants n=108 Participants
Index lesions 2 locations	2 Participants n=8 Participants	28 Participants n=93 Participants	1 Participants n=7 Participants	31 Participants n=108 Participants
Index lesions >= 3 locations	2 Participants n=8 Participants	21 Participants n=93 Participants	2 Participants n=7 Participants	25 Participants n=108 Participants
Prior cancer treatment Chemotherapy only	0 Participants n=8 Participants	4 Participants n=93 Participants	1 Participants n=7 Participants	5 Participants n=108 Participants
Prior cancer treatment Radiotherapy only	0 Participants n=8 Participants	1 Participants n=93 Participants	0 Participants n=7 Participants	1 Participants n=108 Participants
Prior cancer treatment Surgery for primary tumor	1 Participants n=8 Participants	10 Participants n=93 Participants	0 Participants n=7 Participants	11 Participants n=108 Participants
Prior cancer treatment Other / Combinations	2 Participants n=8 Participants	5 Participants n=93 Participants	0 Participants n=7 Participants	7 Participants n=108 Participants
Prior cancer treatment No prior cancer treatment	5 Participants n=8 Participants	73 Participants n=93 Participants	6 Participants n=7 Participants	84 Participants n=108 Participants
Heart rate	76.7 Bpm n=8 Participants	77.7 Bpm n=93 Participants	84.5 Bpm n=7 Participants	78 Bpm n=108 Participants
Systollic blood pressure	120.9 mmHg n=8 Participants	129.7 mmHg n=93 Participants	126.6 mmHg n=7 Participants	128.9 mmHg n=108 Participants
Diastolic blood pressure	68.9 mmHg n=8 Participants	78.8 mmHg n=93 Participants	78.7 mmHg n=7 Participants	78.1 mmHg n=108 Participants

PRIMARY outcome

Timeframe: 9 months

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
PFS Probability Rate at 9 Months in the Dose Escalation Arm	45 percent probability	48 percent probability	0 percent probability	55 percent probability

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Progression Free Survival (PFS) Median Time	8.8 Months Interval 6.2 to 25.6	11.5 Months Interval 8.2 to 14.0	1.3 Months Interval 0.9 to 1.5	10.7 Months Interval 8.1 to 13.7

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=1 Participants 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	Arm B - Standard Dose of Cetuximab n=16 Participants 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.	Not Allocated n=17 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Progression Free Survival (PFS) Median Time for Resected Patients	11.3 Months Interval 0.0 to The upper limit of the 95%CI of the median was not determinable for Arm A.	14.5 Months Interval 12.7 to 17.9	14.2 Months Interval 11.3 to 17.9	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)	1.17 Hazard ratio Interval 0.13 to 10.6	0.82 Hazard ratio Interval 0.48 to 1.42	NA Hazard ratio The hazard ratio and the 95%CI were not determinable for the "Not allocated" patient group.	0.79 Hazard ratio Interval 0.47 to 1.34

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Death Rates by 3 Years Follow-up Lost to follow-up before 3 years followup	0 Participants	12 Participants	0 Participants	12 Participants
Death Rates by 3 Years Follow-up Deceased	6 Participants	65 Participants	7 Participants	78 Participants
Death Rates by 3 Years Follow-up Alive after 3 years follow-up	2 Participants	16 Participants	0 Participants	18 Participants

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Overall Survival (OS) Median Time	28.4 months Interval 12.0 to The upper limit of the 95%CI of the median was not determinable for Arm A.	31.4 months Interval 25.5 to 34.9	4.9 months Interval 1.0 to 12.5	29.8 months Interval 22.4 to 33.3

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=1 Participants 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	Arm B - Standard Dose of Cetuximab n=16 Participants 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.	Not Allocated n=17 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Overall Survival (OS) Median Time for Resected Patients	NA Months The median and the 95%CI of the median were not determinable for Arm A.	NA Months Interval 32.7 to The median and the 95%CI of the median were not determinable for Arm B.	NA Months Interval 32.7 to The median and the 95%CI of the median were not determinable for the ITT set.	—

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Overall Response Other (SD, PD, not evaluable, missing)	2 Participants	29 Participants	7 Participants	38 Participants
Overall Response CR or PR	6 Participants	64 Participants	0 Participants	70 Participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=4 Participants 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	Arm B - Standard Dose of Cetuximab n=39 Participants 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.	Not Allocated n=2 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=45 Participants 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.
Overall Response in Patients With Liver-limited Disease CR or PR	2 Participants	30 Participants	0 Participants	32 Participants
Overall Response in Patients With Liver-limited Disease Other (SD, PD, missing)	2 Participants	9 Participants	2 Participants	13 Participants

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Disease Control CR, PR, or SD	8 Participants	84 Participants	0 Participants	92 Participants
Disease Control Other (PD, not evaluable, missing)	0 Participants	9 Participants	7 Participants	16 Participants

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=4 Participants 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	Arm B - Standard Dose of Cetuximab n=39 Participants 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.	Not Allocated n=2 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=45 Participants 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.
Disease Control in Patients With Liver-limited Disease CR, PR, or SD	4 Participants	37 Participants	0 Participants	41 Participants
Disease Control in Patients With Liver-limited Disease Other (PD, missing)	0 Participants	2 Participants	2 Participants	4 Participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=6 Participants 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	Arm B - Standard Dose of Cetuximab n=64 Participants 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.	Not Allocated n=70 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Duration of Response	8.3 Months Interval 3.6 to 24.2	11.7 Months Interval 9.7 to 14.6	11.7 Months Interval 8.6 to 15.4	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=2 Participants 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	Arm B - Standard Dose of Cetuximab n=30 Participants 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.	Not Allocated n=32 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Duration of Response in Liver-limited Disease Patients	13.9 Months Interval 3.6 to 24.2	11.1 Months Interval 7.6 to 13.0	11.1 Months Interval 7.6 to 22.5	—

SECONDARY outcome

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

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'.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Resections for Metastatic Lesions Non-resected	7 Participants	77 Participants	7 Participants	91 Participants
Resections for Metastatic Lesions Resected (surgery with curative intent performed)	1 Participants	16 Participants	0 Participants	17 Participants

SECONDARY outcome

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

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'.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=1 Participants 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	Arm B - Standard Dose of Cetuximab n=16 Participants 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.	Not Allocated n=17 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
R0 Rate (Free of Tumor After Resection for Metastatic Lesions) Free of tumor	1 Participants	12 Participants	13 Participants	—
R0 Rate (Free of Tumor After Resection for Metastatic Lesions) Not free of tumor	0 Participants	4 Participants	4 Participants	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Skin Toxicity (Safety) Any (onset prior to arm allocation)	2 participants	92 participants	3 participants	—
Skin Toxicity (Safety) Any (all times)	7 participants	93 participants	3 participants	—
Skin Toxicity (Safety) Grade 1	0 participants	19 participants	2 participants	—
Skin Toxicity (Safety) Grade 2	5 participants	44 participants	1 participants	—
Skin Toxicity (Safety) Grade 3	2 participants	30 participants	0 participants	—

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	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.
Laboratory Safety Assessments Hemoglobin decreased	0 participants	3 participants	0 participants	—
Laboratory Safety Assessments White blood cell count decreased	3 participants	8 participants	0 participants	—
Laboratory Safety Assessments Neutrophils decreased	3 participants	19 participants	0 participants	—
Laboratory Safety Assessments Lymphocytes decreased	2 participants	6 participants	0 participants	—
Laboratory Safety Assessments Platelet count decreased	0 participants	2 participants	0 participants	—
Laboratory Safety Assessments Bilirubin increased	0 participants	3 participants	0 participants	—
Laboratory Safety Assessments ALAT increased	0 participants	2 participants	0 participants	—
Laboratory Safety Assessments ASAT increased	0 participants	1 participants	0 participants	—
Laboratory Safety Assessments ALP increased	2 participants	4 participants	0 participants	—
Laboratory Safety Assessments Sodium decreased	1 participants	3 participants	1 participants	—
Laboratory Safety Assessments Potassium decreased	2 participants	7 participants	0 participants	—
Laboratory Safety Assessments Magnesium decreased	1 participants	2 participants	0 participants	—
Laboratory Safety Assessments Magnesium increased	0 participants	1 participants	0 participants	—
Laboratory Safety Assessments Serum calcium decreased	0 participants	2 participants	0 participants	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Arm A - Dose Escalation of Cetuximab n=8 Participants 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	Arm B - Standard Dose of Cetuximab n=93 Participants 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.	Not Allocated n=7 Participants Patients unable to continue treatment with cetuximab and FOLFIRI at standard or reduced doses, requiring discontinuation before arm allocation at day 22.	ITT / Safety Set n=108 Participants 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.
Deaths Till 30 Days From Last Cetuximab Administration Colonic obstruction	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Ileus	0 participants	0 participants	1 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration All causes	1 participants	6 participants	2 participants	9 participants
Deaths Till 30 Days From Last Cetuximab Administration Colonic perforation	1 participants	0 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Malaise	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Bronchial infection	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Lung infection	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Circulatory failure	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Cardiac arrest	0 participants	1 participants	0 participants	1 participants
Deaths Till 30 Days From Last Cetuximab Administration Peritoneal infection	0 participants	0 participants	1 participants	1 participants

Adverse Events

Arm A - Dose Escalation of Cetuximab

Serious events: 6 serious events

Other events: 6 other events

Deaths: 1 deaths

Arm B - Standard Dose of Cetuximab

Serious events: 39 serious events

Other events: 66 other events

Deaths: 6 deaths

Not Allocated

Serious events: 6 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Prof Dr Eric Van Cutsem

UZ Leuven

Phone: 003216344218

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place