Fluorescence Endoscopy of Esophageal Carcinoma (ORCA)

University Medical Center Groningen (UMCG)

Status and phase: Terminated; Phase 1

Conditions: Esophageal Cancer

Treatments: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform

Study type: Interventional

Funder types: Other

Identifiers

NCT03558724

NL65856.042.18

Details and patient eligibility

About

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.

Full description

See brief summary

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

NIR endoscopy with 4.5 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW

NIR endoscopy with 10 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW

NIR endoscopy with 25 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW