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

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

Tracking Information

• First Submitted Date: February 27, 2019
• First Posted Date: March 15, 2019
• Last Update Posted Date: November 4, 2020
• Actual Study Start Date: July 29, 2019
• Estimated Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2019)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 14, 2019)

• 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
• 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
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Detection of Early Esophageal Cancer by NIR-FME.
• Official Title: A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW
• 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.
• Detailed Description: See brief summary
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Barrett Esophagus

Intervention

• 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.

Study Arms

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).

Interventions:

• Drug: Bevacizumab-IRDye800CW
• Diagnostic Test: Fluorescence endoscopy

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 14, 2019): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2021
• Estimated Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03877601
• Other Study ID Numbers: NL68582.042.18
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: dr. W.B. Nagengast, MD, University Medical Center Groningen
• Original Responsible Party: Same as current
• Current Study Sponsor: University Medical Center Groningen
• Original Study Sponsor: Same as current
• Collaborators: Helmholtz Zentrum München

Investigators

• Principal Investigator: W.B. Nagengast, MD, PhD, PharmD; University Medical Center Groningen
• Principal Investigator: Vasilis Ntziachristos, Prof. Dr.; Helmholtz Zentrum München

• PRS Account: University Medical Center Groningen
• Verification Date: November 2020