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

NCT02129933 | Completed Phase 1 DMC

• 2 other identifiers: NL45554.042.142013-003003-19
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer; Dysplasia

Keywords

EAC; HGD; Esophagus

Outcome Measures

Primary Outcomes (1)

• NIR fluorescent signal in vivo (prior to EMR)

  Evaluating presence of specific fluorescent signal in (pre)malignant esophageal lesion in vivo, with use of Near Infrared (NIR) fluorescence endoscopy platform.

  1 day (endoscopy-day)

Secondary Outcomes (4)

• 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

• VEGF expression ex vivo

  up to 1 year

• NIR fluorescent signal in vivo (wound bed, post EMR)

  1 day (endoscopy-day)

• NIR fluorescent signal ex vivo (biopsy and EMR specimen)

  up to 1 year

Study Arms (1)

Tracer bevacizumab-IRDye800CW

EXPERIMENTAL

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

Drug: Bevacizumab-IRDye800CW; Device: Near infrared fluorescence endoscopy platform

Interventions

Bevacizumab-IRDye800CW DRUG

Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW 2 days prior to the fluorescence endoscopy procedure. \* amendment June 2015: topical administration bevacizumab-800CW (100ug/ml)

Also known as: Beva-800CW, Bevacizumab-800CW, Avastin-800CW (Roche)

Tracer bevacizumab-IRDye800CW

Near infrared fluorescence endoscopy platform DEVICE

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 to visualize the luminal wall. The fluorescent imaging will be performed prior and post the endoscopic resection (within the same endoscopic session)

Tracer bevacizumab-IRDye800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (1)

• Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, Koller M, Tjalma JJJ, Karrenbeld A, Jorritsma-Smit A, Kleibeuker JH, van Dam GM, Ntziachristos V. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019 Jan;68(1):7-10. doi: 10.1136/gutjnl-2017-314953. Epub 2017 Dec 15. No abstract available.

  PMID: 29247063 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Wouter B Nagengast, PharmD MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Frans TM Peters, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: May 2, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

NL (1)