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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01051167
Recruitment Status : Completed
First Posted : January 18, 2010
Last Update Posted : May 8, 2017
Information provided by (Responsible Party):
Martin Schuler, Prof. Dr. med., Universität Duisburg-Essen

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Cetuximab Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bi-weekly Cetuximab Combined With FOLFOX-6 as First-line Treatment in Metastatic Colorectal Cancer Patients With Wild-type K-ras Status
Study Start Date : February 2009
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: 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.

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

Primary Outcome Measures :
  1. Response rate (RECIST-Criteria) [ Time Frame: Every 8 weeks ]

Secondary Outcome Measures :
  1. Secondary objectives: Safety, Quality of life [ Time Frame: Every 2 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01051167

University of Duisburg-Essen Medical School
Essen, Nordrhein-Westfalen, Germany, 45122
Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
Essen, Nordrhein-Westfalen, Germany, 45131
Prosper Hospital Recklinghausen
Recklinghausen, Nordrhein-Westfalen, Germany, 45659
Sponsors and Collaborators
Martin Schuler, Prof. Dr. med.
Study Director: Martin Schuler, University of Duisburg-Essen Medical School

Responsible Party: Martin Schuler, Prof. Dr. med., Prof. Dr., Universität Duisburg-Essen Identifier: NCT01051167     History of Changes
Other Study ID Numbers: TT1-2007
2007-000460-24 ( EudraCT Number )
First Posted: January 18, 2010    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs