A Phase II Study Evaluating the Use of Concurrent Cetuximab, Irinotecan, Oxaliplatin and UFT in the First Line Treatment of Patients With Metastatic Colorectal Cancer
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of the colon or rectum.
- Patients must not have a mutation of K-ras
- Inoperable metastatic or locoregional disease (synchronous or recurrence)
- No previous chemotherapy for established metastatic disease (adjuvant chemotherapy
must have been completed more than 6 months prior to trial entry)
- Measurable or evaluable disease
- Bone marrow function: neutrophil count >1.5 x109/l and platelet count >150 x109/l
- Hepatobiliary function: serum bilirubin <1.5 x upper limit of normal (ULN); ALP <5 x
ULN; transaminase (AST or ALT) <3 x ULN.(≤ 5 if liver mets are present)
- Renal function: estimated creatinine clearance >50 ml/min, or measured Glomerular
filtration rate (GFR) (EDTA or creatinine clearance) in normal range
- ECOG performance status 0-1 and considered fit and able to undergo all possible
treatments
- For women of child-bearing potential a negative pregnancy test is required and
adequate contraceptive precautions such as a sheath for their partner must be used
- For men - adequate contraception such as a sheath must be used
- Patients must give written, informed consent
- Life expectancy ≥ 3 months.
Exclusion Criteria:
- Patients that have a K-ras mutation
- Concurrent uncontrolled medical illness, or other previous or current malignant
disease likely to interfere with protocol treatments or comparisons
- Partial or complete bowel obstruction
- Prior EGFR antibody therapy
- Age <18
- Chronic diarrhoea or inflammatory bowel disease
- Known Pyruvate Dehydrogenase Phosphatase (DPD) deficiency
- Gilbert's syndrome or other congenital abnormality of biliary transport
- Previous transplant surgery, requiring immunosuppressive therapy
- Regular / uncontrolled angina or cardiac arrhythmias
- Clinically relevant coronary artery disease. History of Myocardial infarction in the
last 12 months
- Previous investigational agent in the last 4 weeks
- Metastatic disease to brain
- Any pregnant or lactating women
- Patients receiving therapy with haloginated antiviral drugs (eg: sorivudine)
- Patients who have experienced life-threatening toxicities with fluoropyrimidines
treatment
- Patients suffering from any condition that may affect the absorption of UFT or
folinic acid.
- Patients with known deficiency of or are on inhibitors of cytochrome P450 2A6
- Patients who have previously had radiotherapy to the abdomen or pelvis in the last 6
months
- Any medical or psychological condition that in the opinion of the investigator would
not enable the patient to complete the study or knowingly give informed consent