Fluorescence Endoscopy of Esophageal Carcinoma

NCT ID: NCT03558724

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-29
• Study Completion Date: 2022-10-11

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.

Detailed Description

See brief summary

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

NIR endoscopy with 4.5 mg 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 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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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.

NIR endoscopy with 10 mg bevacizumab-800CW

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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.

NIR endoscopy with 25 mg bevacizumab-800CW

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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.

Interventions

Bevacizumab-IRDye800CW

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

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Other Intervention Names

Tracer administration; Fluorescence Endoscopy

Eligibility 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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

W. B. Nagengast, MD, PhD, PharmD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

G. M. van Dam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 25364580 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26287423 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 23026283 (View on PubMed)

Other Identifiers

NL65856.042.18

Identifier Type: -

Identifier Source: org_study_id