Bi-weekly Cetuximab Combined With 5-fluorouracil/Leucovorin/Oxaliplatin (FOLFOX-6) in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— CEBIFOX  

Official title:

Bi-weekly Cetuximab Combined With FOLFOX-6 as First-line Treatment in Metastatic Colorectal Cancer Patients With Wild-type K-ras Status

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01051167
• Other study ID #: TT1-2007
• Secondary ID: 2007-000460-24
• Status: Completed
• Phase: Phase 2
• First received: January 15, 2010
• Last updated: May 3, 2017
• Start date: February 2009
• Est. completion date: September 2016

Study information

• Verified date: May 2017
• Source: Universität Duisburg-Essen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Cetuximab
500 mg /m² cetuximab as an intravenous infusion over 120 minutes on day 1 every 2 weeks

Locations

Country	Name	City	State
Germany	Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH	Essen	Nordrhein-Westfalen
Germany	University of Duisburg-Essen Medical School	Essen	Nordrhein-Westfalen
Germany	Prosper Hospital Recklinghausen	Recklinghausen	Nordrhein-Westfalen

Sponsors (1)

Lead Sponsor	Collaborator
Martin Schuler, Prof. Dr. med.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (RECIST-Criteria)		Every 8 weeks
Secondary	Secondary objectives: Safety, Quality of life		Every 2 weeks