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

NCT ID: NCT02129933

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-11-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Tracer 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

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: 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)

Near infrared fluorescence endoscopy platform

Intervention Type: 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)

Interventions

Bevacizumab-IRDye800CW

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)

Intervention Type: DRUG

Near infrared fluorescence endoscopy platform

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)

Intervention Type: DEVICE

Other Intervention Names

Beva-800CW; Bevacizumab-800CW; Avastin-800CW (Roche)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wouter B Nagengast, PharmD MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Frans TM Peters, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 29247063 (View on PubMed)

Other Identifiers

2013-003003-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL45554.042.14

Identifier Type: -

Identifier Source: org_study_id