Open-label, single-arm, multicenter phase II study of matuzumab in combination with irinotecan background chemotherapy in subjects with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer that developed progressive disease while on therapy or within 4 weeks after termination of an irinotecan based regimen. - MAURICE

• Conditions: Epidermal Growth Factor Receptor (EGFR) expressing, metastatic colorectal cancer; MedDRA version: 7.1Level: LLTClassification code 10052362

• Registration Number: EUCTR2005-001362-14-DE
• Lead Sponsor: Merck KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-05-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

1.Written informed consent provided prior to any prescreening procedure
2.Male or female, 18 years or older
3.Inpatient / Outpatient
4.ECOG performance status of = 2 at study entry
5.Histologically confirmed adenocarcinoma of the colon or rectum
6.Metastatic disease
7.Tissue available for EGFR testing and immunohistochemical evidence of tumor EGFR (HER 1) expression
8.At least 1 bidimensional measurable lesion (not in an irradiated area) according to the modified WHO criteria
9.An irinotecan containing regimen as most recent chemotherapy treatment for at least 6 weeks
10.Documented progression by comparison of CT or MRI scans on irinotecan based therapy whereby the time between documentation of progression and the end of last irinotecan treatment cycle should not be longer than 4 weeks
11.Last application of prior antitumor therapy = 4 weeks
12.Time period from documentation of PD to start of study treatment = 12 weeks
13.Adequate liver, bone marrow, and renal function, defined as:·Bilirubin = 1.5´upper reference range·Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 2.5´ULN (for subjects with liver metastases ALT/AST = 5 ´ ULN)·Neutrophils > 1500 mm3·Platelets > 100,000/µL·Hemoglobin > 10 g/dL·Serum creatinine = 1.5 x ULN or glomerular filtration rate of > 60 mL/minute
14.Recovery from relevant toxicity to previous treatment before study entry
15.Willingness to use contraceptive method for the study duration and 2 months post-dosing.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Previous exposure to epidermal growth factor targeting or epidermal growth factor signaling therapy
2.Previous exposure to VEGF targeting or VEGF-signaling therapy
3.Radiotherapy or major surgery within the last 30 days prior to the start of study treatment
4.Documented or symptomatic brain metastases and/ or central nervous system metastases or leptomeningeal disease
5.Concurrent malignancies or invasive cancers diagnosed within the past 5 years, except for adequately treated basal cell cancer of the skin or in situ cancer of the cervix
6.Known hypersensitivity to matuzumab or irinotecan (according to the current investigators’ brochure for matuzumab and the relevant product information sheets for irinotecan)
7.History of acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
8.Uncontrolled angina pectoris, heart failure, clinically significant uncontrolled cardiac arrhythmias
9.Clinically significant abnormal electrocardiogram (ECG) or cardiac history (e.g. subjects with myocardial infarction within the last 6 months)
10.Significant disease which, in the Investigator’s opinion, would exclude the subject from the study
11.Subject requires concurrent treatment with a non-permitted drug
12.Participation in another clinical study within 30 days before first study treatment
13.Pregnancy (absence to be confirmed by serum ß-hCG test) or lactation period
14.Known alcohol or drug abuse
15.Legal incapacity or limited legal capacity

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Determination of the response rate by the same imaging technique (CT/MRI) that is used consistently for each subject. Classification by modified WHO criteria. The primary analysis variable is the tumor response rate based on response assessments made by an independent radiological review committee.;Main Objective: To determine the response rate of matuzumab in combination with irinotecan background chemotherapy for EGFR-expressing metastatic colorectal cancer which developed PD while on therapy or within 4 weeks after termination of therapy with an irinotecan-based regimen.<br>;Secondary Objective: Progression free survival<br>Duration of response<br>Overall survival time<br>Safety evaluation<br>Determination of HAHA<br>Pharmacokinetics of matuzumab.