Metastatic Colorectal Cancer
Conditions
Brief summary
Cetuximab is normally given as a weekly schedule in the therapy of patients with metastatic colorectal cancer. In order to improve the convenience for the patients in first line-therapy this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX.
Detailed description
For years the effective treatment of advanced colorectal carcinoma (CRC) was limited to fluorouracil (5-FU). Combination of 5-FU or a 5-FU analog with oxaliplatin, which has some antitumor activity as a single agent, shows synergistic activity. Combining oxaliplatin with a twice monthly folinic acid/5-FU schedule leads to a further improvement in first-line treatment of advanced CRC thus emerging to a standard regimen in first-line therapy of metastatic CRC. Cetuximab is normally given as a weekly schedule. As recently shown a biweekly schedule with 500 mg/m² instead of the weekly standard regimen (initial dose of 400 mg/m² followed by 250 mg/m² every week) exhibits similar pharmacokinetic results with a comparable efficacy. In order to improve the convenience for the patients, this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX. Out of the various FOLFOX regimens the most convenient FOLFOX-6 schedule is chosen for the study, which has been tested before in two studies in combination with the standard weekly schedule of cetuximab. Recent data suggest a decreased efficacy of cetuximab in patients bearing a k-ras mutation in their CRC. Therefore only patients with no evidence for a mutated k-ras gene in the colorectal carcinoma cells will be included in this study.
Interventions
DRUGCetuximab
500 mg /m² cetuximab as an intravenous infusion over 120 minutes on day 1 every 2 weeks
Sponsors
Martin Schuler, Prof. Dr. med.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven metastatic colorectal cancer * Molecular test showing no mutation in the k-ras gene of colorectal carcinoma cells * Male and female subjects ≥ 18 years of age * 1st occurrence of metastatic disease (not curatively resectable) * Life expectancy ≥ 12 weeks * Presence of at least 1 bi-dimensionally measurable index lesion (not in an irradiated area) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at study entry * Adequate bone marrow reserve: leucocytes ≥ 3.0 x 109/l with neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l, haemoglobin ≥ 6.21 mmol/l (10 g/dl) * Aspartate-aminotransferase (ASAT) and alanine-aminotransferase (ALAT) ≤ 2.5 x upper reference range, in case of liver metastasis ≤ 5 x upper reference range * Serum creatinine ≤ 1.5 x upper reference range * Bilirubin ≤ 1.5 x upper reference range * Negative pregnancy test for female and effective contraception for both male and female subjects if the risk of conception exists * Signed written informed consent
Exclusion criteria
* Evidence for a mutation of the k-ras gene in the colorectal carcinoma cells * Previous exposure to epidermal growth factor receptor-targeting therapy * Prior chemotherapy for metastatic disease * Prior oxaliplatin based adjuvant chemotherapy or \< 6 months after end of adjuvant treatment * Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix * Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before registration * Concurrent chronic systemic immune therapy or hormone therapy not indicated in this study protocol * Creatinine clearance \< 30 ml/min * Known hypersensitivity reaction to any of the components of study treatment * Pregnancy (absence to be confirmed by ß-human chorionic gonadotropin (hCG) test) or lactation period * Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease * Brain metastasis (known or suspected) * Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent * Known alcohol or drug abuse * Participation in another clinical study within the 30 days before registration * Peripheral neuropathy \> grade 1 * Significant disease which, in the investigator's opinion, would exclude the patient from the study * Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate (RECIST-Criteria) | Every 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives: Safety, Quality of life | Every 2 weeks |
Countries
Germany
Outcome results
None listed