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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00422773
• Other study ID #: TUD-COFI-014
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 15, 2007
• Last updated: February 26, 2009
• Start date: January 2007

Study information

• Verified date: February 2009
• Source: Technische Universität Dresden
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik	Dresden	Sachsen
Germany	Westdeutsches Tumorzentrum, Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität Dresden

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival