Bi-weekly Cetuximab Combined With 5-fluorouracil/Leucovorin/Oxaliplatin (FOLFOX-6) in Metastatic Colorectal Cancer
- Registration Number
- NCT01051167
- Lead Sponsor
- Martin Schuler, Prof. Dr. med.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cetuximab + Folfox-6-regime Cetuximab Cetuximab 500 mg/m² administered as an intravenous infusion over 120 minutes on day 1 every 2 weeks. Combined with the following FOLFOX-6-regime: Oxaliplatin 85 mg/m² i.v. for 2 h on day 1, Folinic acid 400 mg/m² i.v. for 2 h concurrently with Oxaliplatin on day 1, Fluorouracil 400 mg/m² i.v. bolus after Folinic Acid on day 1, followed by Fluorouracil 2400 mg/m² i.v. over 46 h.
- Primary Outcome Measures
Name Time Method Response rate (RECIST-Criteria) Every 8 weeks
- Secondary Outcome Measures
Name Time Method Secondary objectives: Safety, Quality of life Every 2 weeks
Trial Locations
- Locations (3)
University of Duisburg-Essen Medical School
🇩🇪Essen, Nordrhein-Westfalen, Germany
Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
🇩🇪Essen, Nordrhein-Westfalen, Germany
Prosper Hospital Recklinghausen
🇩🇪Recklinghausen, Nordrhein-Westfalen, Germany