erbitux study of cpt11, oxaliplatin, uftoral targeted therapy

Conditions: Metastatic Colorectal Cancer

Summary: a phase ii trial to demonstrate the response rate, using the response evaluation criteria in solid tumours (recist) criteria, of patients with locally advanced / metastatic colorectal cancer treated with combination of irinotecan, oxaliplatin, uft and cetuximab. endpoints primary: objective response rate (recist) secondary: progression free survival (pfs), overall survival (os) toxicity (ctcae), resectability of liver, lung and pelvic disease after chemotherapy, time to progression (ttp). population: the trial aims to recruit 50 patients with inoperable, metastatic colorectal cancer eligibility: histologically confirmed colorectal adenocarcinoma normal haematology and adequate renal and liver function written informed consent and able to attend follow-up for at least 3 months treatment 4 weekly cycles of chemotherapy with alternating irinotecan (day 1) and oxaliplatin(day 15). cetuximab every 2 weeks and oral uft with leucovorin for 3 weeks every 4 weeks. duration first patient recruited april 2009. accrual to take place over 24 months follow-up will continue until death or for a minimum of 3 years


Eligibility criteria:
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