Visualization of Anti-angiogenic Effects With Perfusion Computed Tomography (CTP)

Study Overview
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Brief Summary
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The primary objective of this study is to investigate the anti-angiogenic effect of bevacizumab measured by CTP as a predictive marker for efficacy measured by progression-free survival (PFS) in mCRC patients under first-line bevacizumab-containing, fluoropyrimidine-based chemotherapy

Detailed Description
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So far, CTP has provided non-invasive imaging of tumor biological response to anti-angiogenic and vascular targeting agents in a number of clinical trials with increasing clinical application. CTP can be examined with a variety of commercially available CE-certified CT scanners and imaging post-processing is possible with commercially available CE-certified software from different vendors, too. In several studies, anti-angiogenic effects have been detected with CTP but further evidence for its clinical validation has to be proven in clinical trials. Changes in tumor vasculature measured by CTP will be correlated to the clinical efficacy parameters progression-free survival, overall survival and response rate, thus identifying a group of patients who profit most from the anti-angiogenic treatment.

Official Title
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Visualization of Anti-angiogenic Effects With Perfusion Computed Tomography (CTP) in mCRC Patients Treated With First-line Bevacizumab

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Device: Computed tomography X-ray system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years, male or female Signed written informed consent Patients with histologically confirmed diagnosis of colorectal cancer with hepatic metastases who are candidates for systemic treatment. Confirmation of metastatic liver disease within one month prior to inclusion in one of the following radiological procedures: Contrast-enhanced spiral computed tomography showing at least one liver nodule ≥ 20 mm in longest diameter according to RECIST 1.1 criteria MR imaging of the liver with liver lesions suspicious for metastases PET computed tomography (PET/CT) with liver lesions suspicious for metastases Patient is eligible and designated for treatment with standard-of-care first-line bevacizumab-containing, fluoropyrimidine-based chemotherapy. ECOG performance status ≤ 2 (see appendix) Exclusion Criteria: Inability or unwillingness to comply with the participation requirements History of untreated hyperthyreosis History of intolerance of or allergy to iodine contrast media according to CTCAE V4.03 Calculated creatinine clearance < 45 ml/min For fertile women: positive urine pregnancy test or lactation. Known or suspected non-compliance, drug or alcohol abuse Life expectancy of less than 3 months Participation in another interventional trial with an investigational medicinal product (IMP) and within 30 days prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Perfusion-computed tomography (CTP)<br>Patients undergo a total of four perfusion-computed tomographies from baseline to progression of disease. | Device: Computed tomography X-ray system<br>* Contrast-enhanced computed tomography of liver metastases<br>* Other names: CT scanner;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTP as predictive marker for efficacy measured by progression-free survival | Predictive power of decrease in tumor vasculature on the clinical outcome in bevacizumab-based chemotherapy measured by progression-free survival (PFS). Decrease in tumor vasculature is measured by blood flow in CTP 3 compared to CTP 1 (baseline) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTP as predictive marker for efficacy measured by progression-free survival | Predictive power of decrease in tumor vasculature on the clinical outcome in bevacizumab-based chemotherapy measured by progression-free survival (PFS). Decrease in tumor vasculature is measured by blood flow, blood volume, mean transit time and permeability surface-area product in CTP | one year | 
| CTP as predictive marker for efficacy measured by overall survival | Predictive power of decrease in tumor vasculature measured by CTP on the clinical outcome in bevacizumab-based chemotherapy measured by overall survival (OS) | four years | 
| Tumor vasculature at progression | Tumor vasculature measured by blood flow, blood volume, mean transit time and permeability surface-area product in CTP at the time of confirmed progression | one year | 
| Subgroup analyses according to the RAS mutation status, BRAF mutation status and VEGF-A level | Predictive power of RAS-mutation status, BRAF-mutation status and VEGF-A level on the clinical outcome in bevacizumab-based chemotherapy measured by progression-free survival (PFS) | one year | 
| Local and distant recurrences | Rates of local and distant recurrences according to RECIST 1.1 criteria | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perfusion-computed tomography