Clinical trial NCT02113202: Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adenomatous Polyposis Coli
Keywords: Optical imaging
Fluorescence endoscopy
Near infrared fluorescence
Familial Adenomatous Polyposis
IRDye800CW
Vascular Endothelial Growth Factor A
Gastrointestinal endoscopy
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2014-04-14
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: At surveillance endoscopy
Secondary outcomes:
measure: Meassure the mean fluorescent intensity of the polyps during fluorescence endoscopy, resect the polyps and score VEGF intensity after immunohistochemistry for VEGF.
timeFrame: Two years
measure: Number of participants with Serious Adverse Events as a measure of safety and Tolerability.
timeFrame: Up to 1 week after administration
measure: 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.
timeFrame: Two years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Wouter B Nagengast, PharmD MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Jan Jakob Koornstra, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Jan H Kleibeuker, MD, senior full professor
role: PRINCIPAL_INVESTIGATOR
References: