search
Back to results

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

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
Martin Schuler, Prof. Dr. med.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Duisburg-Essen Medical School
  • Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
  • Prosper Hospital Recklinghausen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cetuximab + Folfox-6-regime

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate (RECIST-Criteria)

Secondary Outcome Measures

Secondary objectives: Safety, Quality of life

Full Information

First Posted
January 15, 2010
Last Updated
May 3, 2017
Sponsor
Martin Schuler, Prof. Dr. med.
search

1. Study Identification

Unique Protocol Identification Number
NCT01051167
Brief Title
Bi-weekly Cetuximab Combined With 5-fluorouracil/Leucovorin/Oxaliplatin (FOLFOX-6) in Metastatic Colorectal Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Martin Schuler, Prof. Dr. med.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab + Folfox-6-regime
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux®
Intervention Description
500 mg /m² cetuximab as an intravenous infusion over 120 minutes on day 1 every 2 weeks
Primary Outcome Measure Information:
Title
Response rate (RECIST-Criteria)
Time Frame
Every 8 weeks
Secondary Outcome Measure Information:
Title
Secondary objectives: Safety, Quality of life
Time Frame
Every 2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Schuler, Prof.Dr.med.
Organizational Affiliation
University of Duisburg-Essen Medical School
Official's Role
Study Director
Facility Information:
Facility Name
University of Duisburg-Essen Medical School
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45131
Country
Germany
Facility Name
Prosper Hospital Recklinghausen
City
Recklinghausen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45659
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32737003
Citation
Kasper S, Meiler J, Knipp H, Hohler T, Reimer P, Steinmetz T, Berger W, Linden G, Reis H, Markus P, Paul A, Dechene A, Schumacher B, Kostbade K, Virchow I, Ting S, Worm K, Schmid KW, Herold T, Wiesweg M, Schuler M, Trarbach T. Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial. Clin Colorectal Cancer. 2020 Dec;19(4):236-247.e6. doi: 10.1016/j.clcc.2020.03.003. Epub 2020 Mar 19.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs