Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases

Study Overview
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Brief Summary
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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: 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. 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: CT scan: RECIST criteria (gold standard); 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: Descriptive analyses; 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 Analysis of prognostic factors: Evaluation of the role of each prognostic factor (pathology and imaging) on response to treatment; Multivariate analysis of prognostic factors; Analysis of the prognostic power of early response at 2 months on the response observed after 6 months of treatment.

Official Title
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Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases

Conditions
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Colorectal Cancer, Neoplasm Metastasis

Intervention / Treatment
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* Drug: cetuximab
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Bevacizumab | Drug: bevacizumab<br>* Indication: first intention treatment<br>* Other names: Avastin;|
| Experimental: 2<br>Cetuximab | Drug: cetuximab<br>* indication : second intention treatment<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elaboration of a predictive model, based on biological and functional imaging parameters, for the response to monoclonal antibodies as assessed through RECIST criteria 2 months after the beginning of treatment |  | at 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the response at 2 months and that at 6 months of treatment (taking into account the therapeutic adjustments during the 6-month follow-up) |  | at 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer,, immunohistochemistry,, monoclonal antibodies,, predictive model,, antiangiogenic agents,, medical imaging, Colorectal cancer with liver metastases