Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases

Study Overview
=================
Brief Summary
-----------------
Bevacizumab, an anti-angiogenic agent, plus fluorouracil based chemotherapy is considered a new standard for the treatment of metastatic colorectal cancer. Contrast-enhanced ultrasound with gas-encapsulated microbubbles can be used to assess tumour vascularity, particularly hepatic metastases, and may become a useful tool for monitoring anti-angiogenic therapies. The aim of this prospective, multicenter, non-randomized study is to evaluate the usefulness of hepatic contrast-enhanced ultrasound to predict response to bevacizumab based chemotherapy in patient with metastatic colorectal cancer. The primary objective of this study is to compare the functional vascular changes related to bevacizumab based chemotherapy and evaluated by hepatic contrast-enhanced ultrasound with classic RECIST criteria. The secondary objectives are to do a characterization of the pharmacokinetic of bevacizumab, to explore the pharmacodynamic effects of bevacizumab on functional vascular changes of hepatic metastases evaluated by hepatic contrast-enhanced ultrasound and to analyze the possible relationships between treatment efficacy or toxicity and constitutional gene polymorphisms linked to the bevacizumab.

Official Title
-----------------
Medical and Economical Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Device: real-time contrast-enhanced ultrasound imaging (CEUS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed colorectal tumor first line treatment by a bevacizumab based chemotherapy Target hepatic metastases of size lower than 5 cm and higher than 5 mm detected by conventional ultrasonography and CT or MRI Life expectancy > 2 months OMS status =< 2 Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0 informed consent signed Exclusion Criteria: no target hepatic lesion detected by conventional ultrasonography Prior bevacizumab treatment Prior chemotherapy treatment for advanced disease Clinically significant cardiac disease (e.g. myocardial infarction or stroke within 12 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure not well controlled with medication, endocarditis and prosthetic valve) and any contraindications in sulphur hexafluoride administration Blood pressure >= 180/110 mmHg Daily and chronic treatment by aspirin or AINS Anticipation of need for major surgical procedure within 7 days prior day 0 Urine protein > 1g/24 Hours Any contraindication in enhancing bevacizumab treatment Serious, uncontrolled, concurrent infection(s) or illness(es) pregnant and lactating woman

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 (single arm)<br>patient with histologically confirmed colorectal tumor treated in first line by a bevacizumab based chemotherapy | Device: real-time contrast-enhanced ultrasound imaging (CEUS)<br>* Real time contrast enhanced sonography was performed using an ultrasound dedicated system after bolus injection of 1.2 and 2x2.4 ml Sonovue ® (Bracco, Milan, Italy)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional vascular changes in tumour vascularity of hepatic metastases |  | 2 months | 
| Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy |  | 2 months | 
| ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound |  | 2 months | 
| evaluation of the response to bevacizumab based chemotherapy by RECIST criteria |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bevacizumab-related toxicity |  | 2 months | 
| response duration |  | 2 years | 
| time to disease progression |  | 2 years | 
| survival time |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal cancer, hepatic metastases, bevacizumab, anti-angiogenic agent, chemotherapy regimens, tumor vascularity, Contrast-enhanced ultrasound