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ORCA: Fluorescence Endoscopy of Esophageal Carcinoma

Sponsor
University Medical Center Groningen (Other)
Overall Status
Recruiting
CT.gov ID
NCT03558724
Collaborator
(none)
38
Enrollment
1
Location
3
Arms
50.1
Anticipated Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

See brief summary

Study Design

Study Type:
Interventional
Anticipated Enrollment :
38 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.
Actual Study Start Date :
Oct 29, 2018
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopy procedure [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.

    2. Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events. [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

    Secondary Outcome Measures

    1. The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results [Up to 1,5 year]

      Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities.

    2. Quantification of the fluorescent signal by MDSFR/SFF spectroscopy [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.

    3. To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE) [Up to 1,5 year]

      CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue

    4. Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy [Up to 1,5 year]

      Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop.

    5. The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence. [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Medical Center Groningen Groningen Netherlands 9713 GZ

    Sponsors and Collaborators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    dr. W.B. Nagengast, MD, Principal investigator, University Medical Center Groningen
    ClinicalTrials.gov Identifier:
    NCT03558724
    Other Study ID Numbers:
    • NL65856.042.18
    First Posted:
    Jun 15, 2018
    Last Update Posted:
    May 20, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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, Principal investigator, University Medical Center Groningen
    Fluorescence
    Endoscopy
    Bevacizumab-800CW
    Locally advanced esophageal cancer
    Additional relevant MeSH terms:
    Esophageal Neoplasms
    Bevacizumab

    Study Results

    No Results Posted as of May 20, 2022