Clinical trial NCT00327093: Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
Official title: Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Colorectal Cancer
Neoplasm Metastasis
Keywords: Colorectal cancer,
immunohistochemistry,
monoclonal antibodies,
predictive model,
antiangiogenic agents,
medical imaging
Colorectal cancer with liver metastases
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2006-05-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: at 7 weeks
Secondary outcomes:
measure: 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)
timeFrame: at 6 month
Other outcomes:
Locations:
city: Lyon
country: France
facility: Jean-Alain Chayvialle
Study officials:
affiliation: Hospices Civils de Lyon
name: Jean-Alain Chayvialle, MD
role: PRINCIPAL_INVESTIGATOR
References: