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Fluorescence Endoscopy of Esophageal Carcinoma (ORCA)

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ClinicalTrials.gov Identifier: NCT03558724
Recruitment Status : Recruiting
First Posted : June 15, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, University Medical Center Groningen

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
Esophageal Cancer Drug: Bevacizumab-IRDye800CW Device: Molecular Fluorescence Endoscopy platform Phase 1

Detailed Description:
See brief summary

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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 : October 29, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: NIR endoscopy with 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 30 patients with locally advanced esophageal cancer
  • 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 mg (microdose) of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Name: 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 Name: Fluorescence Endoscopy




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 [ 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.

  2. 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


Secondary Outcome Measures :
  1. The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results [ Time Frame: Up to 1,5 year ]
  2. 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.

  3. 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

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



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

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;

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): NCT03558724


Contacts
Contact: W. B. Nagengast, MD, PhD, PharmD +31503612620 w.b.nagengast@umcg.nl
Contact: I. Schmidt, MSc +31655256244 i.schmidt@umcg.nl

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: W. B. Nagengast, MD, PhD, PharmD    +31503612620    w.b.nagengast@umcg.nl   
Contact: I. Schmidt, MSc    +31655256244    i.schmidt@umcg.nl   
Principal Investigator: W. B. Nagengast, MD, PhD, PharmD         
Principal Investigator: G. M. van Dam, MD, PhD         
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

Publications:
Responsible Party: dr. W.B. Nagengast, MD, Principal investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03558724     History of Changes
Other Study ID Numbers: NL65856.042.18
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
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, University Medical Center Groningen:
Fluorescence
Endoscopy
Bevacizumab-800CW
Locally advanced esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents