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

Phase 2
18 Years
Open (Enrolling)
Metastatic Colorectal Cancer

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Trial Information

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

For years the effective treatment of advanced CRC was limited to 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 mCRC.

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.

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

- 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)

- ASAT and 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

- 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-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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (RECIST-Criteria)

Outcome Time Frame:

Every 8 weeks

Safety Issue:


Principal Investigator

Tanja Trarbach, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Duisburg-Essen Medical School



Study ID:




Start Date:

February 2009

Completion Date:

September 2014

Related Keywords:

  • Metastatic Colorectal Cancer
  • Colorectal Neoplasms