Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW - Full Text View

Purpose

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.

Condition	Intervention	Phase
Adenomatous Polyposis Coli	Drug: Bevacizumab-IRDye800CW Device: Near infrared fluorescence endoscopy platform	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Visualization of a VEGF-targeted Near-Infrared Fluorescent Tracer in Patients With Familial Adenomatous Polyposis During Fluorescence Endoscopy A Single Center Pilot Intervention Study

Resource links provided by NLM:

Genetics Home Reference related topics: familial adenomatous polyposis

MedlinePlus related topics: Endoscopy

Drug Information available for: Bevacizumab

Genetic and Rare Diseases Information Center resources: Familial Adenomatous Polyposis MYH-associated Polyposis

U.S. FDA Resources

Further study details as provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:

Primary Outcome Measures:

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).

Secondary Outcome Measures:

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?
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)).
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.


Enrollment:	17
Study Start Date:	March 2014
Study Completion Date:	October 2015
Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02113202

Locations


Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ

Sponsors and Collaborators

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

More Information


Responsible Party:	dr. W.B. Nagengast, MD, PharmD MD PhD, University Medical Center Groningen
ClinicalTrials.gov Identifier:	NCT02113202 History of Changes
Other Study ID Numbers:	NL45148.042.13 2013-002490-22 ( EudraCT Number )
Study First Received:	April 2, 2014
Last Updated:	January 8, 2016

Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:


Optical imaging Fluorescence endoscopy Near infrared fluorescence Familial Adenomatous Polyposis	IRDye800CW Vascular Endothelial Growth Factor A Gastrointestinal endoscopy

Additional relevant MeSH terms:


Colorectal Neoplasms Nasopharyngeal Neoplasms Adenomatous Polyposis Coli Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms	Head and Neck Neoplasms Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Adenomatous Polyps Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplastic Syndromes, Hereditary Intestinal Polyposis Genetic Diseases, Inborn Bevacizumab Angiogenesis Inhibitors Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on July 17, 2017

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