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
Overview
- Phase
- Phase 1
- Intervention
- Cetuximab
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Technische Universität Dresden
- Enrollment
- 21
- Locations
- 3
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 17 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Cetuximab+ FOLFOXIRI
Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid
Intervention: Cetuximab
Outcomes
Primary Outcomes
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 Outcomes
- To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival