Barrett EsophagusPhase 2ESCENDNCT03877601
Detection of Early Esophageal Cancer by NIR-FME.
A Phase 2 study testing Bevacizumab-IRDye800CW and Fluorescence endoscopy in people with Barrett Esophagus, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett Esophagus
- What is being tested?
- Bevacizumab-IRDye800CW and Fluorescence endoscopy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- 29 Jul 2019to 1 Oct 2021
- Phase
- Phase 2
- 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
- Suspicion or diagnosed LGD, HGD or superficial EAC and planned diagnostic and/or therapeutic endoscopy.
- Age: 18 years or older.
- Written informed consent.
Who cannot join
- 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
Show all 9Show fewer
- Non-adjustable hypertension
- Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
- Pregnancy or breast feeding.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen
Groningen, 9713 GZ
W B Nagengast, MD, PhD, PharmD, +31503612620, w.b.nagengast@umcg.nl
About this study
Official title: A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW
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.
Read the detailed description
See brief summary
- Conditions
- Barrett Esophagus
- Being tested
- Bevacizumab-IRDye800CW, Fluorescence endoscopy
- Keywords
- Fluorescence, Endoscopy, Bevacizumab-800CW
- Medical subject headings
- Barrett Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab-IRDye800CWDrug
Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.
Fluorescence endoscopyDiagnostic test
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 group | Role | What they receive |
|---|---|---|
| Topical administration of bevacizumab-800CW | Experimental | The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform). Receives: Drug: Bevacizumab-IRDye800CW; Diagnostic Test: Fluorescence endoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fluorescence signal in patients with Barrett's Esophagus
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.
Measured: During the endoscopic procedure
Secondary outcomes (3)
Ex vivo fluorescence singals
Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGF expression
Measured: 2 years
Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR).
Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW
Measured: Up to 1 week after administration of tracer
Interrogate potential new EC biomarkers
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2019
- Study start29 Jul 2019
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Helmholtz Zentrum München
- Responsible party
- Principal investigator, dr. W.B. Nagengast, MD, University Medical Center Groningen
- Investigators
- W.B. Nagengast, MD, PhD, PharmD, Principal investigator, University Medical Center GroningenVasilis Ntziachristos, Prof. Dr., Principal investigator, Helmholtz Zentrum München
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03877601
- Sponsor's protocol ID
- NL68582.042.18
- Acronym
- ESCEND
- Status last verified
- Nov 2020
- First submitted
- 27 Feb 2019
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29247063
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW
- ClinicalTrials.gov ID
- NCT03877601
- Acronym / sponsor ID
- ESCEND / NL68582.042.18
- Conditions
- Barrett Esophagus
- Keywords
- Fluorescence, Endoscopy, Bevacizumab-800CW
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Helmholtz Zentrum München
- Study start
- 29 Jul 2019 (actual)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Oct 2021 (estimated)
- First posted
- 15 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Topical administration of bevacizumab-800CW | Experimental | Drug: Bevacizumab-IRDye800CW, Diagnostic Test: Fluorescence endoscopyThe tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Suspicion or diagnosed LGD, HGD or superficial EAC and planned diagnostic and/or therapeutic endoscopy.
- Age: 18 years or older.
- Written informed consent.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab-IRDye800CWTopical administration of Bevacizumab-IRDye800CW during the endoscopic procedure. | Drug | Topical administration of bevacizumab-800CW |
| Fluorescence endoscopyDevice: 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. | Diagnostic test | Topical administration of bevacizumab-800CW |
Primary outcome
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.
3 secondary outcomes
Ex vivo fluorescence singals
Time frame: 2 years
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
Interrogate potential new EC biomarkers
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Background: PubMed 29247063Nagengast 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W.B. Nagengast, MD, PhD, PharmD principal investigator
University Medical Center Groningen
Vasilis Ntziachristos, Prof. Dr. principal investigator
Helmholtz Zentrum München
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab-IRDye800CW and Fluorescence endoscopy in people with Barrett Esophagus, 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 9 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: status not confirmed, as of the sponsor's last update on 4 Nov 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact W.B. Nagengast, MD, PhD, PharmD (+31503612620, w.b.nagengast@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fluorescence signal in patients with Barrett's Esophagus (time frame: During the endoscopic procedure). 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 NCT03877601, which also lists 1 linked publication.
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 4 Nov 2020.