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

Civil Hospices of Lyon

Status and phase

Terminated

Phase 4

Conditions

Neoplasm Metastasis

Colorectal Cancer

Treatments

Drug: cetuximab

Drug: bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT00327093

2005-401

Details and patient eligibility

About

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:
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.

Enrollment

31 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.