Metastatic Colorectal Cancer
Conditions
Keywords
phase I/II, cetuximab, oxaliplatin, irinotecan, 5-FU, chemotherapy, dose escalation, safety
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.
Interventions
DRUGCetuximab
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
Sponsors
Technische Universität Dresden
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival | — |
Countries
Germany
Outcome results
None listed