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Detection of Early Esophageal Cancer by NIR-FME. (ESCEND)

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ClinicalTrials.gov Identifier: NCT03877601
Recruitment Status : Unknown
Verified November 2020 by dr. W.B. Nagengast, MD, University Medical Center Groningen.
Recruitment status was:  Recruiting
First Posted : March 15, 2019
Last Update Posted : November 4, 2020
Helmholtz Zentrum München
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, 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. 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.

Condition or disease Intervention/treatment Phase
Barrett Esophagus Drug: Bevacizumab-IRDye800CW Diagnostic Test: Fluorescence endoscopy Phase 2

Detailed Description:
See brief summary

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy
Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: Topical administration of bevacizumab-800CW
The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).
Drug: Bevacizumab-IRDye800CW
Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.

Diagnostic Test: Fluorescence endoscopy
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.

Primary Outcome Measures :
  1. Fluorescence signal in patients with Barrett's Esophagus [ Time Frame: During the endoscopic procedure ]
    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.

Secondary Outcome Measures :
  1. Ex vivo fluorescence singals [ Time Frame: 2 years ]
    Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGF expression

  2. Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR). [ Time Frame: Up to 1 week after administration of tracer ]
    Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW

  3. Interrogate potential new EC biomarkers [ Time Frame: 2 years ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Suspicion or diagnosed LGD, HGD or superficial EAC and planned diagnostic and/or therapeutic endoscopy.
  • Age: 18 years or older.
  • Written informed consent.

Exclusion Criteria:

  • Patients younger than 18 years old
  • Submucosal and invasive EAC; EAC with TNM-classification other than T1.
  • Radiation therapy for esophageal cancer
  • Immunoglobulin allergy
  • Chemotherapy, immunotherapy or surgery 28 days before administration of the tracer
  • Prior Bevacizumab treatment
  • Non-adjustable hypertension
  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
  • Pregnancy or breast feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03877601

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Contact: W.B. Nagengast, MD, PhD, PharmD +31503612620 w.b.nagengast@umcg.nl
Contact: R.Y. Gabriels, MSc, MD +31615691998 r.y.gabriels@umcg.nl

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University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: W B Nagengast, MD, PhD, PharmD    +31503612620    w.b.nagengast@umcg.nl   
Sponsors and Collaborators
University Medical Center Groningen
Helmholtz Zentrum München
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Principal Investigator: W.B. Nagengast, MD, PhD, PharmD University Medical Center Groningen
Principal Investigator: Vasilis Ntziachristos, Prof. Dr. Helmholtz Zentrum München
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Responsible Party: dr. W.B. Nagengast, MD, Principal investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03877601    
Other Study ID Numbers: NL68582.042.18
First Posted: March 15, 2019    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:
Additional relevant MeSH terms:
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Esophageal Neoplasms
Barrett Esophagus
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Precancerous Conditions
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors