AzTrials
AzTrials

Esophageal CancerPhase 1ORCANCT03558724

Fluorescence Endoscopy of Esophageal Carcinoma

A Phase 1 study testing Bevacizumab-IRDye800CW and Molecular Fluorescence Endoscopy platform in people with Esophageal Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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%. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
Bevacizumab-IRDye800CW and Molecular Fluorescence Endoscopy platform
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteNetherlands
Study dates
29 Oct 2018to 11 Oct 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

About this study

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.

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.

Read the detailed description

See brief summary

Being tested
Bevacizumab-IRDye800CW, Molecular Fluorescence Endoscopy platform
Keywords
Fluorescence, Endoscopy, Bevacizumab-800CW, Locally advanced esophageal cancer
Medical subject headings
Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bevacizumab-IRDye800CWDrug

    Also called Tracer administration

    Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure

  • Molecular Fluorescence Endoscopy platformDevice

    Also called Fluorescence Endoscopy

    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.

Study groups in NCT03558724
Study groupRoleWhat they receive
NIR endoscopy with 4.5 mg bevacizumab-800CWExperimentalA 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.
Receives: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform
NIR endoscopy with 10 mg bevacizumab-800CWExperimentalA 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.
Receives: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform
NIR endoscopy with 25 mg bevacizumab-800CWExperimentalA 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.
Receives: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.

    Measured: Three days after tracer injection

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

    Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW

    Measured: Up to 14 days after tracer injection

Secondary outcomes (5)

  1. The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results

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

    Measured: Up to 1,5 year

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

    Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo.

    Measured: Up to 1,5 year

  3. To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE)

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

    Measured: Up to 1,5 year

  4. Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy

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

    Measured: 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.

    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.

    Measured: Up to 1,5 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2018
  2. Study start29 Oct 2018
  3. Primary completion11 Oct 2022
  4. Study completion11 Oct 2022

Why it stopped: Dose-escalation was finished, but no clear correlation between fluorescence and tumor grade was established

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03558724
Sponsor's protocol ID
NL65856.042.18
Acronym
ORCA
Status last verified
Apr 2024
First submitted
17 May 2018
Last updated
16 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Duan XF, Tang P, Yu ZT. Neoadjuvant chemoradiotherapy for resectable esophageal cancer: an in-depth study of randomized controlled trials and literature review. Cancer Biol Med. 2014 Sep;11(3):191-201. doi: 10.7497/j.issn.2095-3941.2014.03.005.

    PubMed 25364580

  • Booka E, Takeuchi H, Nishi T, Matsuda S, Kaburagi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Omori T, Kitagawa Y. The Impact of Postoperative Complications on Survivals After Esophagectomy for Esophageal Cancer. Medicine (Baltimore). 2015 Aug;94(33):e1369. doi: 10.1097/MD.0000000000001369.

    PubMed 26287423

  • Raymond D. Complications of esophagectomy. Surg Clin North Am. 2012 Oct;92(5):1299-313. doi: 10.1016/j.suc.2012.07.007.

    PubMed 23026283

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab-IRDye800CW and Molecular Fluorescence Endoscopy platform in people with Esophageal Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Dose-escalation was finished, but no clear correlation between fluorescence and tumor grade was established). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03558724, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.

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