Fluorescence Endoscopy of Esophageal Carcinoma

NCT03558724 | Terminated Phase 1 DMC

• 1 other identifier: NL65856.042.18
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer

Keywords

Fluorescence; Endoscopy; Bevacizumab-800CW; Locally advanced esophageal cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

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

  Up to 1,5 year

• Quantification of the fluorescent signal by MDSFR/SFF spectroscopy

  Up to 1,5 year

• 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

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

  Up to 1,5 year

• 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

Study Arms (3)

NIR endoscopy with 4.5 mg bevacizumab-800CW

EXPERIMENTAL

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; Device: Molecular Fluorescence Endoscopy platform

NIR endoscopy with 10 mg bevacizumab-800CW

EXPERIMENTAL

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; Device: Molecular Fluorescence Endoscopy platform

NIR endoscopy with 25 mg bevacizumab-800CW

EXPERIMENTAL

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; Device: Molecular Fluorescence Endoscopy platform

Interventions

Bevacizumab-IRDye800CW DRUG

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

Also known as: Tracer administration

NIR endoscopy with 10 mg bevacizumab-800CW; NIR endoscopy with 25 mg bevacizumab-800CW; NIR endoscopy with 4.5 mg bevacizumab-800CW

Molecular Fluorescence Endoscopy platform DEVICE

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.

Also known as: Fluorescence Endoscopy

NIR endoscopy with 10 mg bevacizumab-800CW; NIR endoscopy with 25 mg bevacizumab-800CW; NIR endoscopy with 4.5 mg bevacizumab-800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 25364580 BACKGROUND

• 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.

  PMID: 26287423 BACKGROUND

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

  PMID: 23026283 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• W. B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• G. M. van Dam, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 15, 2018
• Study Start: October 29, 2018
• Primary Completion: October 11, 2022
• Study Completion: October 11, 2022
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)