Clinical trial NCT00422773: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: phase I/II
cetuximab
oxaliplatin
irinotecan
5-FU
chemotherapy
dose escalation
safety
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2007-01-17
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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 outcomes:
measure: To assess the treatment regarding the following: feasibility, toxicity, response rate, resection rate, progression free and overall survival
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik
state: Sachsen
city: Essen
country: Germany
facility: Westdeutsches Tumorzentrum, Universitaetsklinikum Essen
city: Mannheim
country: Germany
facility: Universitaetsklinik Mannheim GmbH, III. Medizinische Klinik
Study officials:
affiliation: University Hospital Dresden, Medical Department I
name: Gunnar Folprecht, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.