Fluorescence Endoscopy of Esophageal Carcinoma

Esophageal Cancer Clinical Trial

— ORCA  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03558724
• Other study ID #: NL65856.042.18
• Status: Terminated
• Phase: Phase 1
• Start date: October 29, 2018
• Est. completion date: October 11, 2022

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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%. 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.

Description:

See brief summary

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: October 11, 2022
• Est. primary completion date: October 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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

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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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. Erratum In: Medicine (Baltimore). 2015 Sep;94(39):1. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Three days after tracer injection
Primary	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	Up to 14 days after tracer injection
Secondary	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.	Up to 1,5 year
Secondary	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.	Up to 1,5 year
Secondary	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	Up to 1,5 year
Secondary	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.	Up to 1,5 year
Secondary	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.	Up to 1,5 year