Fluorescence Endoscopy of Esophageal Carcinoma (ORCA)

April 14, 2024 updated by: University Medical Center Groningen

Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.

For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL).

The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

See brief summary

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Locally advanced esophageal carcinoma (cT1b-4a N0-3 M0) in multi-disciplinary esophageal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by esophagectomy;
  • Age ≥ 18 years;
  • Written informed consent.

Exclusion Criteria:

  • Patients with psychological diseases or medical issues who are not able to sign informed consent form;

    • Concurrent uncontrolled medical conditions;
    • Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
    • Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy
    • Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW;
    • History of infusion reactions to bevacizumab or other monoclonal antibodies;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NIR endoscopy with 4.5 mg bevacizumab-800CW

A non-randomized, non-blinded, prospective, feasibility study.

  • IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to a total of 5 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
  • Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:
  • Tracer administration
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. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.
Other Names:
  • Fluorescence Endoscopy
Experimental: NIR endoscopy with 10 mg bevacizumab-800CW

A non-randomized, non-blinded, prospective, feasibility study.

  • IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
  • Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:
  • Tracer administration
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. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.
Other Names:
  • Fluorescence Endoscopy
Experimental: NIR endoscopy with 25 mg bevacizumab-800CW

A non-randomized, non-blinded, prospective, feasibility study.

  • IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
  • Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:
  • Tracer administration
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. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.
Other Names:
  • Fluorescence Endoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopy procedure
Time Frame: Three days after tracer injection
To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy.
Three days after tracer injection
Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events.
Time Frame: Up to 14 days after tracer injection
Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW
Up to 14 days after tracer injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results
Time Frame: Up to 1,5 year
Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities.
Up to 1,5 year
Quantification of the fluorescent signal by MDSFR/SFF spectroscopy
Time Frame: Up to 1,5 year
Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo.
Up to 1,5 year
To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE)
Time Frame: Up to 1,5 year
CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue
Up to 1,5 year
Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy
Time Frame: Up to 1,5 year
Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop.
Up to 1,5 year
The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence.
Time Frame: Up to 1,5 year
Both the images and specific measurements are used to calculate the fluorescence intensity (TBR & intrinsic fluorescence) and a difference between the before and after intensity is calculated.
Up to 1,5 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: W. B. Nagengast, MD, PhD, PharmD, University Medical Center Groningen
  • Principal Investigator: G. M. van Dam, MD, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 29, 2018

Primary Completion (Actual)

October 11, 2022

Study Completion (Actual)

October 11, 2022

Study Registration Dates

First Submitted

May 17, 2018

First Submitted That Met QC Criteria

June 14, 2018

First Posted (Actual)

June 15, 2018

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 14, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL65856.042.18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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