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

Phase 4

Terminated

• Conditions: Colorectal Cancer; Neoplasm Metastasis
• Interventions: Drug: bevacizumab; Drug: cetuximab

• Registration Number: NCT00327093
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05
• Study First Submitted: 2006-05-17
• Study First Submitted QC: 2006-05-17
• Study First Posted: 2006-05-18
• Primary Completion: 2008-10
• Study Completion: 2008-10
• Status Verified: 2009-02
• Last Update Submitted: 2009-02-06
• Last Update Posted: 2009-02-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	bevacizumab	Bevacizumab
2	cetuximab	Cetuximab

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Jean-Alain Chayvialle; 🇫🇷 Lyon, France