Colorectal Cancer, Neoplasm Metastasis
Conditions
Keywords
Colorectal cancer,, immunohistochemistry,, monoclonal antibodies,, predictive model,, antiangiogenic agents,, medical imaging, Colorectal cancer with liver metastases
Brief 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.
Interventions
DRUGcetuximab
indication : second intention treatment
DRUGbevacizumab
Indication: first intention treatment
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
France
Outcome results
None listed