Safety and Efficacy Study of Combination Therapy With Cetuximab and FOLFOX4 in Patients With Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine confirmed objective response rate to combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with CRC and non-resectable hepatic metastases

Official Title
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Open-label, Phase II, Randomised, Pilot Study to Evaluate the Safety and Efficacy of Combination Therapy With Cetuximab and FOLFOX4 or FOLFOX4 Alone in Patients Colorectal Cancer and Initially Non-resectable

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOX-4+cetuximab
* Drug: FOLFOX-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Men and women < 75 years Histologically confirmed diagnosis of CRC Metastatic colorectal carcinoma with exclusive non-resectable hepatic metastases, due to fulfillment of one of the following criteria: Number of hepatic metastases > or= 4; Size of one or more hepatic metastases > 5 cm diameter; Vascular involvement and/or poor site that prevent complete resection of hepatic disease and/or require resection with the remaining liver mass less than 25-30% of functional liver. Presence of at least one lesion detectable by two-dimensional measurement. Karnofsky functional status >or=70% at the time of enrollment in study Life expectancy greater than 3 months. Patients must not have received chemotherapy for advanced/metastatic disease. Patients with the following characteristics will be enrolled: Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free period > 6 months following conclusion of treatment. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment. De novo diagnosis of disease. Proper liver function, defined by aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < or = 2.5 x ULN (< or = 5 x ULN if there are hepatic metastases) and total bilirubin count < 1.5 x ULN. Proper kidney function, defined as serum creatinine < 1.5 x ULN. Proper hematological function, defined as neutrophil count > or = 1.5 x 109/l , platelets > or = 100 X 109/l and hemoglobin > or = 9 g/dl. Effective birth control method for men as well as women if there is possibility of pregnancy Exclusion Criteria: Documented or suspected cerebral and/or leptomeningeal metastases. Metastasis in any other non-hepatic site, including extrahepatic lymph node metastases. Surgery (excluding biopsy for diagnosis) and/or radiotherapy within 4 weeks prior to enrollment in the study. Participation in another clinical trial with medication in the past 30 days. Chronic, concomitant administration of systemic immunotherapy, chemotherapy, hormone therapy or any other investigational drug. Prior malignant tumour in past 5 years, except history of basal cell skin carcinoma or pre-invasive cervical carcinoma. Any investigational drug during the 4 weeks prior to enrolment. Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment. Prior participation in study in which treatment with cetuximab can be assigned (whether or not treatment with cetuximab is received) Acute or subacute intestinal occlusion or history of inflammatory intestinal disease. Evidence of grade 3 or 4 allergic reaction to any of the treatment components. Clinically relevant peripheral neuropathy. Clinically relevant myocardial disease or history of myocardial infarction in the past 12 months. Known abuse of alcohol / drugs, Legal incapacity or limited legal capacity. Any medical or psychological disorder which, in the opinion of the investigator, does not allow the patient to conclude the study or sign the informed consent. Pregnant or nursing woman

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>FOLFOX-4+cetuximab | Drug: FOLFOX-4+cetuximab<br>* Cetuximab; Weekly administration of Cetuximab IV (initial infusion of 400 mg/m2 for 120 minutes followed by subsequent maintenance doses of 250 mg/m2 for 60 minutes); FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2<br>|
| Active Comparator: 2<br>FOLFOX-4 | Drug: FOLFOX-4<br>* FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine confirmed objective response rate |  | 2005-2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine safety of combination, surgical resectability and R0 resections, clinical benefit, time to disease progression, time to onset of response, duration of response, time to treatment failure, overall survival time |  | 2005-2009 | 
| determination of polymorphisms of the intron 1 of the EGFR gene, TS, XRCC1, XPD, serum levels of EGFR and ATP7A and ATP7B, nº of copies of EGFR gene, the levels of PTEN, EGFR, AKT y MAPK proteins, and mutations at EGFR, PI3KCA, K-RAS y B-RAF genes |  | 2005-2009 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, cetuximab, FOLFOX4