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

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring phase I/II, cetuximab, oxaliplatin, irinotecan, 5-FU, chemotherapy, dose escalation, safety

Eligibility Criteria

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

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

Sites / Locations

  • Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik
  • Westdeutsches Tumorzentrum, Universitaetsklinikum Essen
  • Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cetuximab+ FOLFOXIRI

Arm Description

Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid

Outcomes

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

Full Information

First Posted
January 15, 2007
Last Updated
February 26, 2009
Sponsor
Technische Universität Dresden
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1. Study Identification

Unique Protocol Identification Number
NCT00422773
Brief Title
Safety of Cetuximab and Oxaliplatin/5-FU/FA/Irinotecan in First-Line Treatment of Metastatic Colorectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2009
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Technische Universität Dresden

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
phase I/II, cetuximab, oxaliplatin, irinotecan, 5-FU, chemotherapy, dose escalation, safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab+ FOLFOXIRI
Arm Type
Experimental
Arm Description
Cetuximab and Irinotecan, Oxaliplatin, 5FU and Folinic acid
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Cetuximab (C225, Erbitux by Merck)
Intervention Description
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
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunnar Folprecht, Dr.
Organizational Affiliation
University Hospital Dresden, Medical Department I
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Westdeutsches Tumorzentrum, Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
45112
Country
Germany
Facility Name
Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik
City
Mannheim
ZIP/Postal Code
68167
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
25038824
Citation
Folprecht G, Hamann S, Schutte K, Trarbach T, Stoehlmacher-Williams J, Ehninger G. Dose escalating study of cetuximab and 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) in first line therapy of patients with metastatic colorectal cancer. BMC Cancer. 2014 Jul 19;14:521. doi: 10.1186/1471-2407-14-521.
Results Reference
derived

Learn more about this trial

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

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