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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00327093
• Other study ID #: 2005-401
• Status: Terminated
• Phase: Phase 4
• First received: May 17, 2006
• Last updated: February 6, 2009
• Start date: May 2006
• Est. completion date: October 2008

Study information

• Verified date: February 2009
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• cetuximab
indication : second intention treatment
• bevacizumab
Indication: first intention treatment

Locations

Country	Name	City	State
France	Jean-Alain Chayvialle	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No