CompletedNCT01251536Everest2Updated Oct 11, 2019Results posted

Cetuximab Standard or Dose Escalation in First Line Colorectal Cancer

A Phase 2 interventional study of Dose escalation of cetuximab and Standard first line treatment with cetuximab + Folfiri in Colorectal Cancer, sponsored by Universitaire Ziekenhuizen KU Leuven. Completed at 30 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-11.

Sponsored by Universitaire Ziekenhuizen KU Leuven · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 108
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The purposes of this study are to determine whether administering escalating doses of cetuximab in patients with no early skin toxicity could delay the progression of disease in a significant proportion of patients and to study the molecular signatures of response.

Read the detailed description

Colorectal carcinoma (CRC) is the third most common form of cancer worldwide and remains a leading malignancy both in incidence and mortality.

In the light of existing knowledge, the investigators propose a phase II open label, two arm study in patients presenting with K-Ras wild-type metastatic colorectal tumours in the first line setting. The standard combination of irinotecan plus infusional 5-FU/LV (FOLFIRI) and cetuximab will be given to all patients entering the study. As the investigators hypothesize that increasing the dose of cetuximab might increase the intensity of skin reactions that directly correlates with outcome, in patients experiencing no skin toxicity, the dose of cetuximab will be escalated from 250 mg/m2 to 350 mg/m2 and then up to 500 mg/m2, in order to better define the effect of dose escalation in the first-line setting in a K-Ras wild type tumour population and in an attempt to increase efficacy.

Pharmacokinetic studies will be performed to document PK parameters of cetuximab in patients from both arms in selected centers.

Translational research studies are planned for all patients. Some more in depth molecular testing will be performed in a subset of patients from whom three serial tissue samples from accessible metastases by biopsy are available.

Conditions studied

Colorectal Cancer

Browse trials for

Colorectal Neoplasms 5,599

Keywords

colorectal cancer
K-Ras wildtype
first line metastatic
standard cetuximab + FOLFIRI
dose escalation cetuximab

In context

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's enrollment of 108 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Browse Colorectal Neoplasms studies →

Lead sponsor

Universitaire Ziekenhuizen KU Leuven is the lead sponsor of 928 studies on the registry; 261 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Written informed consent (+ optional for PK and TR) must be given according to ICH/GCP and national/local regulations.
Patient is at least 18 years of age.
Patient's body weight is ≤ 120 kg.
Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon or rectum, not in a previously irradiated area.
K-Ras wild type tumour eligible for treatment with cetuximab.
Unresectable metastatic disease.
Life expectancy of at least 12 weeks.
WHO ECOG performance status: 0 or 1.
Effective contraception for both male and female patients if the risk of conception exists.
Adequate organ function.
Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry):
- Hemoglobin > 10.0 g/dL, absolute neutrophil count > 1.5 x 109/L, platelet count > 100 x 109/L
- ALAT, ASAT \< 2.5 x ULN, up to \< 5 x ULN in case of liver metastases
- Alkaline phosphatase \< 2.5 x ULN
- Total bilirubin \< 1.5 x ULN
- Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)

Exclusion criteria

Exclusion Criteria:

Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 6 months prior to registration on study).
Prior treatment with EGFR inhibitor or chemotherapy with irinotecan in adjuvant settings.
Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry.
Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment.
Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol.
Any active dermatological condition > grade 1.
Brain metastasis (known or suspected).
Significant impairment of intestinal absorption (e.g. chronic diarrhea, inflammatory bowel disease).
Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
Uncontrolled coronary artery disease and/or unstable angina, a history of a myocardial infarction within the last 12 months or heart failure NYHA class III or IV. High risk of uncontrolled arrhythmia.
Known allergy or any other adverse reaction to any of the drugs or to any related compound.
Known dihydropyrimidine dehydrogenase (DPD) deficiency.
Gilbert disease.
Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
Organ allografts requiring immunosuppressive therapy.
Pregnancy (absence confirmed by serum/urine beta human choriongonadotrophin in pre-menopausal women) or breast-feeding.
Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 108 participants (actual)

Study arms

Other
Arm B - standard dose of cetuximab
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
Experimental
Arm A - dose escalation of cetuximab
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

Interventions

DrugDose 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
Also known as: Erbitux
DrugStandard 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.
Also known as: Erbitux

What researchers measure

Primary outcomes

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.
Time frame: 9 months

Secondary outcomes

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).
Time frame: Treatment + follow-up (3 years from database lock)
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.
Time frame: Treatment + follow-up (3 years from database lock)
Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)
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.
Time frame: Treatment + follow-up (3 years from database lock)
Death Rates by 3 Years Follow-up
Deaths by 3 years follow-up after last cetuximab administration + 30 days. All patients (ITT).
Time frame: Treatment + follow-up (3 years from database lock)
Overall Survival (OS) Median Time
Overall survival was considered from start of treatment to death. All patients (ITT).
Time frame: Treatment + follow-up (3 years from database lock)
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.
Time frame: Treatment + follow-up (3 years from database lock)
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).
Time frame: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
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.
Time frame: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
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).
Time frame: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
Disease Control in Patients With Liver-limited Disease
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). Subset of patients with liver-limited disease.
Time frame: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
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.
Time frame: Treatment + follow-up (3 years from database lock)
Duration of Response in Liver-limited Disease Patients
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 among patients with liver-limited disease.
Time frame: Treatment + follow-up (3 years from database lock)
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'.
Time frame: Treatment + follow-up (3 years from database lock)
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'.
Time frame: Treatment + follow-up (3 years from database lock)
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.
Time frame: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.
Laboratory Safety Assessments
Severe laboratory abnormalities (hematology and biochemistry grade 3 and higher). Worst grade per patient. All patients treated (Safety set).
Time frame: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.
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.
Time frame: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.

Results

Posted Oct 11, 2019

Limitations and caveats

Insufficient population in escalation arm A as early skin toxicity in most patients; study not powered for formal comparison between arms. Systematic error sources: some AEs re-coded by sponsor, misclassification bias (local response assessment).

Participant flow

Participant flow — Overall Study
Milestone	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated
Started	8	93	7
Completed	8	93	7
Not completed	0	0	0

Outcome measures

PrimaryPFS 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.

Time frame:: 9 months
Reported as:: Number · percent probability

PFS Probability Rate at 9 Months in the Dose Escalation Arm
percent probability	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
PFS Probability Rate at 9 Months in the Dose Escalation Arm	45	48	0	55

SecondaryProgression 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).

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · Months

Progression Free Survival (PFS) Median Time
Months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
Progression Free Survival (PFS) Median Time	8.8 (6.2 to 25.6)	11.5 (8.2 to 14)	1.3 (0.9 to 1.5)	10.7 (8.1 to 13.7)

SecondaryProgression 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.

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · Months

Progression Free Survival (PFS) Median Time for Resected Patients
Months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	ITT / Safety Set
Progression Free Survival (PFS) Median Time for Resected Patients	11.3 (0 to NA)	14.5 (12.7 to 17.9)	14.2 (11.3 to 17.9)

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

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Number · Hazard ratio

Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)
Hazard ratio	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)	1.17 (0.13 to 10.6)	0.82 (0.48 to 1.42)	NA (NA to NA)	0.79 (0.47 to 1.34)

SecondaryDeath Rates by 3 Years Follow-up

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

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Count of participants · Participants

Death Rates by 3 Years Follow-up
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
Deceased	6	65	7	78
Alive after 3 years follow-up	2	16	0	18
Lost to follow-up before 3 years followup	0	12	0	12

SecondaryOverall Survival (OS) Median Time

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

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · months

Overall Survival (OS) Median Time
months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
Overall Survival (OS) Median Time	28.4 (12 to NA)	31.4 (25.5 to 34.9)	4.9 (1.0 to 12.5)	29.8 (22.4 to 33.3)

SecondaryOverall 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.

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · Months

Overall Survival (OS) Median Time for Resected Patients
Months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	ITT / Safety Set
Overall Survival (OS) Median Time for Resected Patients	NA (NA to NA)	NA (32.7 to NA)	NA (32.7 to NA)

SecondaryOverall 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).

Time frame:: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
Reported as:: Count of participants · Participants

Overall Response
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
CR or PR	6	64	0	70
Other (SD, PD, not evaluable, missing)	2	29	7	38

SecondaryOverall 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.

Time frame:: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
Reported as:: Count of participants · Participants

Overall Response in Patients With Liver-limited Disease
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
CR or PR	2	30	0	32
Other (SD, PD, missing)	2	9	2	13

SecondaryDisease 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).

Time frame:: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
Reported as:: Count of participants · Participants

Disease Control
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
CR, PR, or SD	8	84	0	92
Other (PD, not evaluable, missing)	0	9	7	16

SecondaryDisease Control in Patients With Liver-limited Disease

Time frame:: Treatment duration (interval from first infusion to last infusion on study for each patient), an average of 8.5 months.
Reported as:: Count of participants · Participants

Disease Control in Patients With Liver-limited Disease
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
CR, PR, or SD	4	37	0	41
Other (PD, missing)	0	2	2	4

SecondaryDuration 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.

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · Months

Duration of Response
Months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	ITT / Safety Set
Duration of Response	8.3 (3.6 to 24.2)	11.7 (9.7 to 14.6)	11.7 (8.6 to 15.4)

SecondaryDuration of Response in Liver-limited Disease Patients

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Median · Months

Duration of Response in Liver-limited Disease Patients
Months	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	ITT / Safety Set
Duration of Response in Liver-limited Disease Patients	13.9 (3.6 to 24.2)	11.1 (7.6 to 13.0)	11.1 (7.6 to 22.5)

SecondaryResections 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'.

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Count of participants · Participants

Resections for Metastatic Lesions
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
Resected (surgery with curative intent performed)	1	16	0	17
Non-resected	7	77	7	91

SecondaryR0 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'.

Time frame:: Treatment + follow-up (3 years from database lock)
Reported as:: Count of participants · Participants

R0 Rate (Free of Tumor After Resection for Metastatic Lesions)
Participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	ITT / Safety Set
Free of tumor	1	12	13
Not free of tumor	0	4	4

SecondarySkin 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.

Time frame:: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.
Reported as:: Number · participants

Skin Toxicity (Safety)
participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated
Any (onset prior to arm allocation)	2	92	3
Any (all times)	7	93	3
Grade 1	0	19	2
Grade 2	5	44	1
Grade 3	2	30	0

SecondaryLaboratory Safety Assessments

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

Time frame:: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.
Reported as:: Number · participants

Laboratory Safety Assessments
participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated
Hemoglobin decreased	0	3	0
White blood cell count decreased	3	8	0
Neutrophils decreased	3	19	0
Lymphocytes decreased	2	6	0
Platelet count decreased	0	2	0
Bilirubin increased	0	3	0
ALAT increased	0	2	0
ASAT increased	0	1	0
ALP increased	2	4	0
Sodium decreased	1	3	1
Potassium decreased	2	7	0
Magnesium decreased	1	2	0
Magnesium increased	0	1	0
Serum calcium decreased	0	2	0

SecondaryDeaths 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.

Time frame:: From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.
Reported as:: Number · participants

Deaths Till 30 Days From Last Cetuximab Administration
participants	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	ITT / Safety Set
All causes	1	6	2	9
Colonic perforation	1	0	0	1
Malaise	0	1	0	1
Bronchial infection	0	1	0	1
Lung infection	0	1	0	1
Circulatory failure	0	1	0	1
Cardiac arrest	0	1	0	1
Colonic obstruction	0	1	0	1
Peritoneal infection	0	0	1	1
Ileus	0	0	1	1

Adverse events

Collected over From signature of informed consent to last cetuximab administration on study plus 30 days for each patient, an average of 9.5 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm A - Dose Escalation of Cetuximab	1/8 (12.5%)	6/8 (75%)	6/8 (75%)
Arm B - Standard Dose of Cetuximab	6/93 (6.5%)	39/93 (41.9%)	66/93 (71%)
Not Allocated	2/7 (28.6%)	6/7 (85.7%)	3/7 (42.9%)

Most frequent serious events

Showing 10 of 38

Most frequent serious events
Event	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated
DiarrheaGastrointestinal disorders	2/8	2/93	1/7
Thromboembolic eventVascular disorders	0/8	8/93	1/7
Ischemia cerebrovascularNervous system disorders	0/8	0/93	1/7
FeverGeneral disorders	1/8	0/93	1/7
Colonic perforationGastrointestinal disorders	1/8	1/93	1/7
IleusGastrointestinal disorders	0/8	1/93	1/7
Small intestinal obstructionGastrointestinal disorders	0/8	3/93	1/7
Peritoneal infectionInfections and infestations	0/8	0/93	1/7
FatigueGeneral disorders	1/8	1/93	0/7
Jejunal obstructionGastrointestinal disorders	1/8	0/93	0/7

Most frequent other events

Showing 10 of 62

Most frequent other events
Event	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated
DiarrheaGastrointestinal disorders	2/8	14/93	0/7
HypokalemiaMetabolism and nutrition disorders	2/8	2/93	0/7
ParonychiaInfections and infestations	2/8	1/93	0/7
Rash acneiformSkin and subcutaneous tissue disorders	0/8	17/93	0/7
SyncopeNervous system disorders	0/8	1/93	1/7
Abdominal painGastrointestinal disorders	0/8	1/93	1/7
Colonic perforationGastrointestinal disorders	1/8	1/93	1/7
Small intestinal obstructionGastrointestinal disorders	0/8	2/93	1/7
Peritoneal infectionInfections and infestations	0/8	0/93	1/7
Peripheral sensory neuropathyNervous system disorders	1/8	0/93	0/7

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
<=18 years	0	0	0	0
Between 18 and 65 years	2	69	5	76
>=65 years	6	24	2	32

Age, Continuous
Age, Continuous(years)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
Median	66 (57 to 76)	60 (30 to 79)	64 (58 to 77)	60 (30 to 79)

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
Female	5	24	1	30
Male	3	69	6	78

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
Count of participants	—	—	—	0

Region of Enrollment
Region of Enrollment(participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
Austria	0	4	0	4
Belgium	6	18	0	24
Hungary	0	20	2	22
France	0	5	2	7
Spain	2	46	3	51

Primary tumour
Primary tumour(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
Colon right	2	16	0	18
Colon left	2	47	5	54
Rectum	4	30	2	36

Tumour stage
Tumour stage(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
T1	0	2	0	2
T2	0	2	0	2
T3	2	46	2	50
T4	4	27	4	35
Tx	2	16	1	19

Nodal stage
Nodal stage(Participants)	Arm A - Dose Escalation of Cetuximab	Arm B - Standard Dose of Cetuximab	Not Allocated	Total
N0	2	7	2	11
N1	0	24	0	24
N2	3	34	2	39
Nx	3	28	3	34

7 further baseline measures are reported on the registry.

Study locations

30 sites

Universitätsklinik für Innere medizin, Klinishe abteilung für hämatologie und Onkologie
Innsbruck, Austria
LKH Leoben, abteilung f. innere Medizin
Leoben, Austria
AKH Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinishe Onkologie
Linz, Austria
Landeskrankenhaus Salzburg, Univ. Klinik für innere Medizin III, Universitätsklinikum der PMU
Salzburg, Austria
Krankenanstalt Rudolfstiftung, 1 medizinishe Abteilung
Wien, Austria
St Vincent Krankenhaus Betriebs GmbH
Zams, Austria
Imelda Ziekenhuis
Bonheiden, Belgium
Erasme Hospital
Brussels, 1070, Belgium
Cliniques Universitaires St Luc
Brussels, 1200, Belgium
AZ Middelares Gent
Gent, Belgium
UZ Gent
Gent, Belgium
Centre Hospitalier de Jolimont-Lobbes, Oncology Médicale
Haine Saint Paul, Belgium
AZ Groeninge
Kortrijk, 8500, Belgium
UZ Gasthuisberg
Leuven, 3000, Belgium
CHC Saint Joseph
Liege, Belgium
AZ Sint Maarten Mechelen/Duffel
Mechelen, Belgium
H. Hartziekenhuis
Roeselare, 8800, Belgium
AZ Turnhout (Campus St Elisabeth)
Turnhout, Belgium
Hôpital Avicennes
Bobigny, France
Hôpital Saint-André
Bordeaux, 33000, France
Hopital Européen Georges Pompidou
Paris, 75015, France
Centre Eugène Marquis
Rennes Cedex, 35042, France
CHU Charles Nicolle
Rouen, 76031, France
State Health Center
Budapest, 1062, Hungary
Medical Center of the University of Pecs , National Institute Oncology
Budapest, 1122, Hungary
Hospital Universitari Vall d'Hebron
Barcelona, 8035, Spain
Institut Català d'Oncologia
Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Hospital Universitario Virgen del Rocío
Sevilla, Spain
Hospital Clinico Universitario De Valencia
Valencia, Spain

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 11, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01251536
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Collaborators: Merck KGaA, Darmstadt, Germany
Responsible party: Sponsor
First posted: Dec 2, 2010
Start date: Dec 2010
Primary completion: Jun 2016
Completion: Jul 2019
Results posted: Oct 11, 2019
Last update: Oct 11, 2019

Study contacts

Eric Van Cutsem, MD

principal investigator · UZ Leuven

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.

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