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

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

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

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:

  1. Number of hepatic metastases > or= 4;
  2. Size of one or more hepatic metastases > 5 cm diameter;
  3. 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:

  1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free period > 6 months following conclusion of treatment.
  2. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment.
  3. 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