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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Open Labeled, Multicenter Phase I/II Study Evaluating the Dose Escalation/Safety of Cetuximab and Oxaliplatin/5-FU/FA/Irinotecan as First-Line Treatment of Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab+ FOLFOXIRI<br>Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid | Drug: Cetuximab<br>* Dose level Infusion time (h) Dose level unit 1 2 3 4 Cetuximab 2.0 mg/m² 500 500 500 500 Irinotecan, before oxaliplatin 1.0 mg/m² 95 125 165 180 Oxaliplatin, with folinic acid 2.0 mg/m² 85 85 85 85 Folinic acid, with folinic acid 2.0 mg/m² 400 400 400 400 5-FU Infusion 46.0 mg/m² 3200 3200 3200 3200<br>* Other names: Cetuximab (C225, Erbitux by Merck);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phase I/II, cetuximab, oxaliplatin, irinotecan, 5-FU, chemotherapy, dose escalation, safety