Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW (FLUOFAP)

October 24, 2023 updated by: University Medical Center Groningen

Visualization of a VEGF-targeted Near-Infrared Fluorescent Tracer in Patients With Familial Adenomatous Polyposis During Fluorescence Endoscopy A Single Center Pilot Intervention Study

There is a need for better visualization of polyps during surveillance endoscopy in patients with hereditary colon cancer syndromes like Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS), to improve the adenoma detection rate. Optical molecular imaging of adenoma associated biomarkers is a promising technique to accommodate this need. The biomarker Vascular Endothelial Growth Factor (VEGF) is overexpressed in adenomatous colon tissue versus normal tissue and has proven to be a valid target for molecular imaging. The University Medical Center Groningen (UMCG) developed a fluorescent tracer by labeling the VEGF-targeting humanized monoclonal antibody bevacizumab, currently used in anti-cancer therapy, with the fluorescent dye IRDye800CW. The investigators hypothesize that when bevacizumab-IRDye800CW is administered to patients, it accumulates in VEGF expressing adenomas, enabling adenoma visualization using a newly developed near-infrared (NIR) fluorescence endoscopy platform (NL43407.042.13). This hypothesis will be tested in this feasibility study, next to the determination of the optimal tracer dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with genetically or clinically proven Familial Adenomatous Polyposis. Genetically proven: Adenomatous Polyposis Coli (APC)-mutation identified. Clinically proven: more than 100 colorectal polyps at diagnosis
  • Age 18 to 70 years
  • Written informed consent
  • Adequate potential for follow-up

Exclusion Criteria:

  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent
  • Proctocolectomy
  • MutYH mutation
  • Concurrent uncontrolled medical conditions
  • Pregnant or lactating women. Documentation of a negative pregnancy test must be available for woman of childbearing potential. Woman of childbearing potential are pre-menopausal women with intact reproductive organs and women less than two years after menopause.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tracer dose: 4.5 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 4.5 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.
Experimental: Tracer dose: 10 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 10 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.
Experimental: Tracer dose: 25 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 25 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of fluorescent adenomatous polyps during surveillance endoscopy using the near-infrared fluorescence endoscopy platform in patients with Familial Adenomatous Polyposis (FAP), after administration of the fluorescent tracer bevacizumab-IRDye800CW.
Time Frame: At surveillance endoscopy
The main objective of this study is to determine the sensitivity of the fluorescent tracer bevacizumab-IRDye800CW and the near-infrared fluorescence endoscopy platform in identifying adenomatous polyps during surveillance endoscopy in patients with Familial Adenomatous Polyposis (FAP).
At surveillance endoscopy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Meassure the mean fluorescent intensity of the polyps during fluorescence endoscopy, resect the polyps and score VEGF intensity after immunohistochemistry for VEGF.
Time Frame: Two years
In this outcome meassure, it is determined if there is a correlation between the observed mean fluorescence intensity of a polyp and the VEGF expression in the same polyp, as determined with immunohistochemistry and eventually RNA/DNA analysis. In other words, does the mean fluorescence intensity reflect the VEGF expression of the polyp?
Two years
Number of participants with Serious Adverse Events as a measure of safety and Tolerability.
Time Frame: Up to 1 week after administration
Collection of safety data regarding administration of Bevacizumab-IRDye800CW (adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)).
Up to 1 week after administration
Measure the mean fluorescent intensity of adenomas and compare this between the three different dosing groups to determine the best tracer dose for the fluorescence endoscopy procedure.
Time Frame: Two years
The goal of this outcome measure, is to determine the optimal tracer dose (4.5, 10 or 25 mg) of bevacizumab-IRDye800CW for the molecular-guided fluorescence endoscopy procedure to visualize adenomas. The fluorescence intensity of adenomas will be measured in vivo during fluorescence endoscopy and ex vivo (e.g. using confocal fluorescence microscopy, spectroscopy). This will be compared between the three subgroups (patients with different time intervals between tracer injection and endoscopy procedure) to determine the best time interval between tracer injection and endoscopy procedure.
Two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: Wouter B Nagengast, PharmD MD PhD, University Medical Center Groningen
  • Principal Investigator: Jan Jakob Koornstra, MD PhD, University Medical Center Groningen
  • Principal Investigator: Jan H Kleibeuker, MD, senior full professor, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

April 2, 2014

First Submitted That Met QC Criteria

April 11, 2014

First Posted (Estimated)

April 14, 2014

Study Record Updates

Last Update Posted (Actual)

October 27, 2023

Last Update Submitted That Met QC Criteria

October 24, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL45148.042.13
  • 2013-002490-22 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Adenomatous Polyposis Coli

Clinical Trials on Bevacizumab-IRDye800CW

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe