Bi-weekly Cetuximab Combined With FOLFOX-6 as First-line Treatment in Metastatic Colorectal Cancer Patients With Wild-type K-ras Status
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 59
- Locations
- 3
- Primary Endpoint
- Response rate (RECIST-Criteria)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Cetuximab + Folfox-6-regime
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.
Intervention: Cetuximab (Drug)
Outcomes
Primary Outcomes
Response rate (RECIST-Criteria)
Time Frame: Every 8 weeks
Secondary Outcomes
- Secondary objectives: Safety, Quality of life(Every 2 weeks)
Investigators
Martin Schuler, Prof. Dr. med.
Prof. Dr.
Universität Duisburg-Essen