Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Barrett Esophagus

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Precancerous Conditions

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).

Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.

Bevacizumab-IRDye800CW

Device: Molecular Fluorescence Endoscopy platform A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope.

Fluorescence endoscopy

W.B. Nagengast, MD, PhD, PharmD

R.Y. Gabriels, MSc, MD

W B Nagengast, MD, PhD, PharmD

Vasilis Ntziachristos, Prof. Dr.

To improve detection of esophageal (pre)malignant lesions during surveillance endoscopy of patients at risk of developing malignancies, for example in Barrett's Esophagus (BE), there is a need for better endoscopic visualization and the ability for targeted biopsies. Optical molecular imaging of neoplasia associated biomarkers could form a promising technique to accommodate this need. It is known that the biomarker Vascular Endothelial Growth Factor (VEGF) is overexpressed in dysplastic and neoplastic areas in BE segments 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 phase I study, named VICE, completed within the UMCG, showed that synchronal use of VEGFA-guided near-infrared fluorescence molecular endoscopy (NIR-FME) and high-definition white light endoscopy (HD-WLE), following topical or systemic tracer administration, could be practiced to recognize dysplastic and early EAC lesions in patients with BE. Furthermore, early lesion detection was improved by \~33% using the topically applied tracer approach compared with HD-WL/NBI endoscopy. With this phase 2 intervention study the investigators aim to statistically confirm previous pilot (Phase I) clinical data showing that the combination of HD-WLE and FME using labelled bevacizumab improves early EC detection over the current clinical standard.

Detection of Early Esophageal Cancer by NIR-FME.

A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW

Evaluating the performance of FME with topical administration of Bevacizumab-800CW for detection of neoplasia in BE patients compared to HD-WLE to make an estimation of the diagnostic accuracy in terms of sensitivity and specificity in order to make a power size calculation for the Phase III trial.

Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGF expression

Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW

We will perform ex-vivo binding experiments with tracers against GREM1, -SULF1 and -PRKCi on the fresh EMR if available and compare them against the in-vivo WLE/NIR-FME findings. We will analyze the sensitivity and specificity of the novel markers alone or in combination. The targeting moieties will be coupled with different fluorophores allowing for multi-parametric analysis.

Helmholtz Zentrum München

University Medical Center Groningen

Principal investigator

Diseases and Abnormalities at or Before Birth

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Adenomatous Polyposis Coli

Colorectal Neoplasms

Nasopharyngeal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Polyps

Adenomatous Polyps

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Intestinal Polyposis

Genetic Diseases, Inborn

Familial Adenomatous Polyposis

MYH-associated Polyposis

Endothelial Growth Factors

Mitogens

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.

Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 10 mg of the fluorescent tracer bevacizumab-IRDye800CW.

Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 25 mg of the fluorescent tracer 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.

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.

Near infrared fluorescence endoscopy platform

Wouter B Nagengast, PharmD MD PhD

Jan Jakob Koornstra, MD PhD

Jan H Kleibeuker, MD, senior full professor

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.

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

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

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).

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?

Collection of safety data regarding administration of Bevacizumab-IRDye800CW (adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)).

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Detection of Early Esophageal Cancer by NIR-FME.	NCT03877601	Barrett Esophag...	Bevacizumab-IRD... Fluorescence en...	18 Years -	University Medical Center Groningen
Detection of Early Esophageal Cancer by NIR-FME.	NCT03877601	Barrett Esophag...	Bevacizumab-IRD... Fluorescence en...	18 Years -	University Medical Center Groningen
Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW	NCT02113202	Adenomatous Pol...	Bevacizumab-IRD... Near infrared f...	18 Years - 70 Years	University Medical Center Groningen
Detection of Early Esophageal Cancer by NIR-FME.	NCT03877601	Barrett Esophag...	Bevacizumab-IRD... Fluorescence en...	18 Years -	University Medical Center Groningen

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