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
- 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
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
- Documented or suspected cerebral and/or leptomeningeal metastases.
- Metastasis in any other non-hepatic site, including extrahepatic lymph node
- 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
- 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