Safety of Cetuximab and Oxaliplatin/5-FU/FA/Irinotecan in First-Line Treatment of Metastatic Colorectal Cancer

Phase 1

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Cetuximab

• Registration Number: NCT00422773
• Lead Sponsor: Technische Universität Dresden

Brief Summary

The purpose of this study is to assess a maximal tolerable dose and to assess the safety of a chemotherapy-combination of cetuximab, irinotecan, oxaliplatin and 5-fluorouracil (5-FU)/folinic acid (FA) as first-line treatment for metastatic colorectal cancer.

Detailed Description

Dose escalation:

The first three patients will receive chemotherapy at the dose level 1 for 6 weeks (first three cycles). The dose will be escalated for the next patients by one dose level if none of the three patients at a dose level experience a dose-limiting toxicity (DLT) during the first six weeks. If one of the three patients has a DLT, an additional three patients will be enrolled at this dose level and the dose will be escalated if no additional patients experience a DLT. Otherwise, the dose escalation will be stopped, and the last dose will be regarded as the maximum tolerated dose (MTD). An intra-individual dose escalation is not planned.

Expanded cohort:

The MTD cohort will be expanded to a total of 16 patients.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-01-15
• Study First Submitted QC: 2007-01-15
• Study First Posted: 2007-01-17
• Primary Completion: 2008-06
• Status Verified: 2009-02
• Last Update Submitted: 2009-02-26
• Last Update Posted: 2009-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Diagnosis of non-resectable, histologically confirmed, epithelial growth factor receptor(EGFR)-positive or negative colorectal cancer
• WHO Performance status 0 or 1
• Signed written informed consent
• ≥ 18 years of age
• Effective contraception for both male and female subjects if the risk of conception exists
• Adequate bone marrow function: neutrophil blood cell count (NBC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, hemoglobin ≥ 5.96 mmol/L (10 g/dL)
• Adequate liver and renal function: bilirubin ≤ 1.5 x upper normal level (UNL) and not increasing more than 25% within the last 4 weeks; ASAT and ALAT ≤ 5 x UNL; serum creatinine ≤ 1.5 x UNL.

Exclusion Criteria

• Previous exposure to epidermal growth factor receptor-targeting therapy
• Previous chemotherapy for colorectal cancer except for adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment or 5-FU in combination with radiotherapy for rectal cancer
• Radiotherapy or major abdominal or thoracic surgery within the last 4 weeks before inclusion.
• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy.
• Investigational agents or participation in clinical trials within 30 days before start of the treatment in study.
• Clinically relevant coronary disease or myocardial infarction within 12 months before study entry.
• Peripheral neuropathy > CTC (Common Toxicity Criteria)grade I
• Inflammatory bowel disease
• Previous malignancy (except for colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
• History of severe psychiatric illness
• Drug or alcohol abuse
• Known hypersensitivity reaction to any of the components of study treatment
• Pregnancy (absence to be confirmed by b-hCG (pregnancy-) test) or lactation period
• Brain metastasis and/or leptomeningeal disease (known or suspected)
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cetuximab+ FOLFOXIRI	Cetuximab	Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid

Primary Outcome Measures

Name	Time	Method
To assess a maximal tolerable dose and the safety of a chemotherapy-combination of cetuximab, irinotecan, oxaliplatin and 5-FU/folinic acid as first-line treatment for metastatic colorectal cancer

Secondary Outcome Measures

Name	Time	Method
To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival

Trial Locations

Locations (3)

Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik; 🇩🇪 Mannheim, Germany

Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik; 🇩🇪 Dresden, Sachsen, Germany

Westdeutsches Tumorzentrum, Universitaetsklinikum Essen; 🇩🇪 Essen, Germany