elaboration of a model for predicting efficacy of monoclonal antibodies (cetuximab and bevacizumab) in patients with colorectal cancer and liver metastases

Conditions: Colorectal Cancer; Neoplasm Metastasis

Summary: primary objective: this trial is elaborating a model for rapidly predicting (day 21) the response to monoclonal antibodies anti-egfr and anti-vegf (cetuximab and bevacizumab) based on biological markers and/or functional imaging. the response to treatment is evaluated by the conventional method after 2 months (response evaluation criteria in solid tumors \[recist\] criteria). secondary objectives: 1. this trial is also analyzing the correlation between the magnitude of response to treatment at 2 months (stabilization or objective response, recist criteria) and that of response observed after 6 months of treatment. 2. the organisational objective is to develop a tumour bank of metastatic colorectal cancer. population: the population includes 252 male and female patients with metastatic colorectal cancer justifying the use of cetuximab or bevacizumab, with no heart disease. techniques: computed tomography (ct scan), functional imaging (ultrasound with sonovue); molecular imaging (positron emission tomography \[pet\] with fluorodeoxyglucose f18 \[18-fdg\]); and biology and pathology on microbiopsy of liver metastasis are used. outcome criteria: the primary outcome is response to treatment with monoclonal antibodies according to recist criteria at two months. studied factors: radiology: 1. ct scan: recist criteria (gold standard); 2. ultrasound with sonovue injection: 1 representative target (delay of contrast appearance, peak of rising, curve of increase and decrease of the signal, area under the curve, time of average transit). nuclear medicine: pet scan and 18-fdg (standard uptake values \[suv\]) molecular characterization of tumors: p53 status; microsatellite instability (msi) status; expression of oncogenes; egfr status; vegf status; determination of fcgammariiia polymorphisms statistics: 1. descriptive analyses; 2. analysis of the appropriate threshold to measure: response to treatment by an ultrasound with sonovue and by pet scan; correlation between response predicted by the ultrasound with sonovue and the pet; conventional morphological ct at 2 months 3. analysis of prognostic factors: 1. evaluation of the role of each prognostic factor (pathology and imaging) on response to treatment; 2. multivariate analysis of prognostic factors; 3. analysis of the prognostic power of early response at 2 months on the response observed after 6 months of treatment.


Eligibility criteria:
inclusion criteria: * patients \>= 18 years old * patients with colon or rectal carcinoma histologically proven * patients with metastases (synchronous or metachronous) * patients with associated extra-hepatic disease (asymptomatic primary tumor or extra-hepatic metastases) * performance status (world health organization \[who\]) = 0, 1, or 2 * life expectancy \>= 3 months * patients with normal haematological, kidney, and liver parameters (pnn \> 1.5 x 10\^9/l, platelets \> 100 10\^9/l, total bilirubin \<= 1.25 x upper limit of normal (uln), asat/alat \<= 5 x uln, creatinaemia \<= 135 µmol/l (1.5 mg/dl) * no cardiac or coronary insufficiency untreated * at least 4 weeks between surgery and study beginning * patients can have a biopsy of the hepatic lesion identified by ultrasound. * informed consent signed. exclusion criteria: * patients with symptomatic tumors (colon or rectal) * patients with others tumors not cured * patients who cannot be treated by 5-fluorouracil (5-fu) and/or irinotecan because of special medical conditions or other serious disease. * patients who participated in another clinical trial since less than 30 days * pregnancy or breast-feeding women * patients who cannot be treated because of active infection or other serious disease.

Keywords: colorectal cancer, immunohistochemistry, monoclonal antibodies, predictive model, antiangiogenic agents, medical imaging colorectal cancer with liver metastases