Determining the safety and feasibility of optical coherence tomography and near infrared fluorescence: a prospective pilot intervention study

To improve detection of premalignant lesions in the gastrointestinal tract (the
rectum and the esophagus) there is a need for better endoscopic visualization
and the ability for targeted biopsies. The University Medical Center Groningen
(UMCG) developed a fluorescent tracer by labelling the VEGF-A*targeting
humanized monoclonal antibody bevacizumab, currently used in anti-cancer
therapy, with the fluorescent dye IRDye800CW (Bevacizumab-800CW). In several
phase I studies and phase II studies, either completed or currently running, in
the UMCG, the use of VEGF-A-guided near-infrared (NIR) fluorescence molecular
endoscopy (FME) in combination with high-definition white light endoscopy
(HD-WLE) shows an improved detection rate of early premalignant lesions. In
this study the safety and feasibility of a next generation imaging system will
be tested. This system uses immune optical coherence tomography (immuno-OCT)
and near infrared fluorescence (NIRF) with the targeted tracer
(Bevacizumab-800CW) for improvement of the detection of dysplastic lesions in
Barret*s esophagus (BE) and colorectal polyp detection. The system provides
more depth information and can eventually be used without the guidance of the
regular endoscopy system.

- Primary: Determine safety and feasibility of immuno-OCT in vivo imaging with
the tracer Bevacizumab-800CW.
- Secondary: Validate the immuno-OCT endoscopy system based on:
o Fluorescence molecular endoscopy;
o Ex vivo fluorescence imaging;
o Ex vivo immuno-OCT imaging;
o Immunohistochemistry.

The current study is a non-randomized, non-blinded, prospective and
single-center feasibility and safety study. Patients in the UMCG known with BE
or colorectal polyps and scheduled for endoscopic resection will be included in
this study. The primary endpoint of this study is the determination of the
safety and feasibility of the immuno-OCT system.

Patients scheduled for an endoscopic resection and eligible for this study will
receive information about this study through the phone or when visiting the
out-patient clinic. When patients are willing to participate in the study they
will receive an intravenous administration of Bevacizumab-800CW below
therapeutic dosage, two to four days before the endoscopy procedure or they
will receive topical administration of bevacizumab-800CW. Vital signs will be
measured before, directly after and ten minutes after injection. The endoscopy
procedure will consist of three phases. First the patient will receive standard
clinical care with HD-WLE in which all visible suspicious and malignant lesions
will be identified. In the next phase, FME will be applied and suspicious
fluorescent areas will be inspected by HD-WLE. Thirdly, immuno-OCT will be
applied. Biopsies will be taken to allow ex vivo correlation. The complete
procedure will take an extra 15 - 25 minutes compared to regular care. During
the procedure and measurements videos will be recorded which will be used for
further analysis. During the intervention the patient is under sedation. If a
patient with esophageal lesions is included in the topical administration
cohort, phase 2 and 3 will be performed immediately after application of the
tracer (using a spraying catheter) and following incubation (5 minutes) and
rinsing off the excess tracer with water. The concentration per cm2 will be
controllable and results will therefore be comparable.

Time investment
Compared to standard care, one extra visit to the UMCG of about 20 minutes is
needed when the patient receives IV administration. Regular procedure time is
about 1 hour and will take 15 - 25 minutes longer due to our study.

Risks
The administration risks of Bevacizumab-800CW are reported in the
Investigational Medicinal Product Dossier (version 6.0). The intravenous
injection and the use of a cannula are known to carry a small risk of infection
and hematoma. No adverse events were reported from previous administrations
with Bevacizumab-800CW with more than 235 patients included. However, injection
of Bevacizumab-800CW could induce an allergic reaction or hypertension. Due to
fluorescence imaging and immuno-OCT, the endoscopy will be prolonged for 15 -
25 minutes. As the fiber of FME can be inserted through the working channel of
the HD-WL endoscope, the risks of fluorescence imaging are comparable to HD-WL
endoscopy. The fiber of immuno-OCT can be inserted in a similar way to the
regular endoscope also minimizing the risks. The biopsy procedure may cause
some bleeding which can often be treated by the gastroenterologist.

Benefit
There is no direct diagnostic or treatment benefit for the patients as all
procedures are following standard clinical guidance. No decisions according to
clinical care will be based on study results.