VEGF-targeted Fluorescence Near-Infrared (NIR) Endoscopy in (Pre)Malignant Esophageal Lesions

Phase 1

Completed

• Conditions: Esophageal Cancer; Dysplasia
• Interventions: Drug: Bevacizumab-IRDye800CW; Device: Near infrared fluorescence endoscopy platform

• Registration Number: NCT02129933
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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. We hypothesize that when bevacizumab-IRDye800CW is administered, it accumulates in VEGF expressing high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), enabling early cancer visualization using a newly developed fluorescent NIR fiber-bundle. This hypothesis will be tested in this pilot intervention study.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-24
• Study First Submitted QC: 2014-04-30
• Study First Posted: 2014-05-02
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-14
• Last Update Posted: 2024-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Identified HGD or intramucosal EAC (T1) and therefore candidate for endoscopic mucosal resection therapy
• Mentally competent person, 18 years or older.
• Written informed consent.
• Adequate potential for follow-up.

Exclusion Criteria

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Submucosal and invasive EAC; EAC with tumor-classification other than T1.
• Concurrent (uncontrolled) medical conditions which disqualify for an endoscopic mucosal resection procedure.
• Previously performed therapeutic endoscopic procedures.
• Pregnancy or breast feeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tracer bevacizumab-IRDye800CW	Bevacizumab-IRDye800CW	Two days prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform), all patients will receive the fluorescent tracer bevacizumab-IRDye800CW intravenously. \*amendement June 2015: topical administration of bevacizumab-800CW
Tracer bevacizumab-IRDye800CW	Near infrared fluorescence endoscopy platform	Two days prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform), all patients will receive the fluorescent tracer bevacizumab-IRDye800CW intravenously. \*amendement June 2015: topical administration of bevacizumab-800CW

Primary Outcome Measures

Name	Time	Method
NIR fluorescent signal in vivo (prior to EMR)	1 day (endoscopy-day)	Evaluating presence of specific fluorescent signal in (pre)malignant esophageal lesion in vivo, with use of Near Infrared (NIR) fluorescence endoscopy platform.

Secondary Outcome Measures

Name	Time	Method
VEGF expression ex vivo	up to 1 year	Correlation between specific fluorescent signal in vivo and ex vivo (observed with near-infrared fluorescence endoscopy) and VEGF expression ex vivo (immunohistochemistry).
NIR fluorescent signal in vivo (wound bed, post EMR)	1 day (endoscopy-day)	Presence of specific fluorescence signal in correlation to histological evaluation of specimen (resection margins)
NIR fluorescent signal ex vivo (biopsy and EMR specimen)	up to 1 year	Evaluation of specific fluorescent signal ex vivo in correlation with observed fluorescence signal during endoscopy procedure.
Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR).	Two days prior and up to 1 week after administration of tracer	Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands