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

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

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

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Device: Computed tomography X-ray system

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • GR
    • Chur, GR, Switzerland, 7000
      • Kantonsspital Graubünden
  • LU
    • Luzern, LU, Switzerland, 6000
      • Luzerner Kantonsspital
  • SG
    • St. Gallen, SG, Switzerland, 9007
      • Kantonsspital St. Gallen
  • ZH
    • Winterthur, ZH, Switzerland, 8401
      • Kantonsspital Winterthur
    • Zürich, ZH, Switzerland, 8091
      • UniversitätsSpital Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Patrick Veit-Haibach
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Patrick Veit-Haibach, MD, University Hospital Zurich, Diagnostic and Interventional Radiology

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Perfusion-computed tomography
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: KEK-ZH-Nr. 2015-0084