Safety of Cetuximab and Oxaliplatin/5-FU/FA/Irinotecan in First-Line Treatment of Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by:
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00422773
First received: January 15, 2007
Last updated: February 26, 2009
Last verified: February 2009
  Purpose

The purpose of this study is to assess a maximal tolerable dose and to assess the safety of a chemotherapy-combination of cetuximab, irinotecan, oxaliplatin and 5-fluorouracil (5-FU)/folinic acid (FA) as first-line treatment for metastatic colorectal cancer.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Cetuximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Labeled, Multicenter Phase I/II Study Evaluating the Dose Escalation/Safety of Cetuximab and Oxaliplatin/5-FU/FA/Irinotecan as First-Line Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • To assess a maximal tolerable dose and the safety of a chemotherapy-combination of cetuximab, irinotecan, oxaliplatin and 5-FU/folinic acid as first-line treatment for metastatic colorectal cancer

Secondary Outcome Measures:
  • To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival

Estimated Enrollment: 21
Study Start Date: January 2007
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab+ FOLFOXIRI
Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid
Drug: Cetuximab
Dose level Infusion time (h) Dose level unit 1 2 3 4 Cetuximab 2.0 mg/m² 500 500 500 500 Irinotecan, before oxaliplatin 1.0 mg/m² 95 125 165 180 Oxaliplatin, with folinic acid 2.0 mg/m² 85 85 85 85 Folinic acid, with folinic acid 2.0 mg/m² 400 400 400 400 5-FU Infusion 46.0 mg/m² 3200 3200 3200 3200
Other Name: Cetuximab (C225, Erbitux by Merck)

Detailed Description:

Dose escalation:

The first three patients will receive chemotherapy at the dose level 1 for 6 weeks (first three cycles). The dose will be escalated for the next patients by one dose level if none of the three patients at a dose level experience a dose-limiting toxicity (DLT) during the first six weeks. If one of the three patients has a DLT, an additional three patients will be enrolled at this dose level and the dose will be escalated if no additional patients experience a DLT. Otherwise, the dose escalation will be stopped, and the last dose will be regarded as the maximum tolerated dose (MTD). An intra-individual dose escalation is not planned.

Expanded cohort:

The MTD cohort will be expanded to a total of 16 patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of non-resectable, histologically confirmed, epithelial growth factor receptor(EGFR)-positive or negative colorectal cancer
  • WHO Performance status 0 or 1
  • Signed written informed consent
  • ≥ 18 years of age
  • Effective contraception for both male and female subjects if the risk of conception exists
  • Adequate bone marrow function: neutrophil blood cell count (NBC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, hemoglobin ≥ 5.96 mmol/L (10 g/dL)
  • Adequate liver and renal function: bilirubin ≤ 1.5 x upper normal level (UNL) and not increasing more than 25% within the last 4 weeks; ASAT and ALAT ≤ 5 x UNL; serum creatinine ≤ 1.5 x UNL.

Exclusion Criteria:

  • Previous exposure to epidermal growth factor receptor-targeting therapy
  • Previous chemotherapy for colorectal cancer except for adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment or 5-FU in combination with radiotherapy for rectal cancer
  • Radiotherapy or major abdominal or thoracic surgery within the last 4 weeks before inclusion.
  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy.
  • Investigational agents or participation in clinical trials within 30 days before start of the treatment in study.
  • Clinically relevant coronary disease or myocardial infarction within 12 months before study entry.
  • Peripheral neuropathy > CTC (Common Toxicity Criteria)grade I
  • Inflammatory bowel disease
  • Previous malignancy (except for colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
  • History of severe psychiatric illness
  • Drug or alcohol abuse
  • Known hypersensitivity reaction to any of the components of study treatment
  • Pregnancy (absence to be confirmed by b-hCG (pregnancy-) test) or lactation period
  • Brain metastasis and/or leptomeningeal disease (known or suspected)
  • Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00422773

Locations
Germany
Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik
Dresden, Sachsen, Germany, 01307
Westdeutsches Tumorzentrum, Universitaetsklinikum Essen
Essen, Germany, 45112
Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik
Mannheim, Germany, 68167
Sponsors and Collaborators
Technische Universität Dresden
Investigators
Principal Investigator: Gunnar Folprecht, Dr. University Hospital Dresden, Medical Department I
  More Information

No publications provided by Technische Universität Dresden

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gunnar Folprecht, University Hospital Dresden, Medical Department I
ClinicalTrials.gov Identifier: NCT00422773     History of Changes
Other Study ID Numbers: TUD-COFI-014
Study First Received: January 15, 2007
Last Updated: February 26, 2009
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Technische Universität Dresden:
phase I/II
cetuximab
oxaliplatin
irinotecan
5-FU
chemotherapy
dose escalation
safety

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Cetuximab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014