Fluorescence Image Guided Surgery in Cholangiocarcinoma

NCT03620292 | Unknown Phase 1

• 1 other identifier: NL65378.042.18
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Cholangiocarcinoma is an epithelial cell malignancy arising from varying locations within the biliary tree and is difficult to diagnose due to the often-silent clinical nature. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. Because cholangiocarcinoma is difficult to diagnose at an early stage and extends diffusely, most patients have unresectable disease at clinical presentation, and prognosis is very poor (5-year survival is 0-40% even in resected cases) There is a need for better visualization of tumor tissue, lymph nodes and resection margins during surgery for perihilar cholangiocarcinoma (PHCC). Optical molecular imaging of PHCC associated biomarkers is a promising technique to accommodate this need. The biomarkers Vascular Endothelial Growth Factor (VEGF-A), Epidermal Growth Factor Receptor (EGFR) and c-MET are all overexpressed in PHCC versus normal tissue and are proven to be valid targets for molecular imaging. Currently, tracers that target these biomarkers are available for use in clinical studies. In previous studies with other tumor types, the investigators tested the tracer bevacizumab-IRDye800CW for the biomarker VEGF-A with very promising results. Since all markers show roughly similar expression in ex vivo studies, the initial study will be performed with bevacizumab-IRDye800CW as the investigators have the most experience with this tracer. The investigators hypothesize that the tracer bevacizumab-IRDye 800CW accumulates in PHCC tissue, enabling visualization using a NIR intraoperative camera system and ex vivo NIR endoscopy. In this pilot study, the investigators will determine if it is possible to detect PHCC intraoperatively and by ex vivo NIR endoscopy using bevacizumab 800CW, and which tracer dose gives the best target-to-background ratio. The most optimal tracer dose will be selected for a future phase II trial.

Conditions

Hilar Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Optimal dose finding of Bevacizumab 800CW in hilar cholangiocarcinoma

  \- Comparison of three doses of Bevacizumab 800CW by calculating target to background ratios in fluorescence images obtained during and directly after the surgical procedure and fluorescence images obtained during ex vivo analyses in bread loaf slices and in histological slices (odyssey scanner, fluorescence microscopy).

  24 months

Secondary Outcomes (4)

• Peroperative detection of hilar cholangiocarcinoma with real-time near-infrared fluorescence camera

  24 months

• Detection of hilar cholangiocarcinoma in real-time near-infrared fluorescence ex-vivo endoscopy

  24 months

• Establish tracer distribution in tumour tissue

  24 months

• Measurement of fluorescence in tumour tissue en surrounding normal tissue

  24 months

Study Arms (1)

Intraoperative NIR fluorescence imaging

EXPERIMENTAL

A non-randomized, non-blinded, prospective, single center pilot dose escalation study with bevacizumab-800CW for NIR fluorescence image guided surgery in hilar cholangiocarcinoma * IV-administration of 10, 25 or 50 mg of the fluorescent tracer bevacizumab-800CW to a total of 15 patients with resectable hilar cholangiocarcinoma 3 days prior to surgery. * Peroperative open air NIR fluorescence imaging * Ex vivo endoscopic and histopathological NIR fluorescence imaging

Drug: Bevacizumab-IRDye800CW; Device: near infrared (NIR) fluorescence imaging

Interventions

Bevacizumab-IRDye800CW DRUG

Intravenous administration of Bevacizumab-IRDye800CW prior to surgery for hilar cholangiocarcinoma

Also known as: Tracer administration

Intraoperative NIR fluorescence imaging

near infrared (NIR) fluorescence imaging DEVICE

Intraoperative NIR fluorescence imaging of hilar cholangiocarcinoma, lymph nodes, resection margins, resection specimens

Also known as: optical imaging

Intraoperative NIR fluorescence imaging

Eligibility Criteria

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

You may qualify if:

• Patients with clinical suspicion of PHCC who are scheduled to undergo surgical intervention with curative intent
• WHO performance score 0-2.

You may not qualify if:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Other invasive malignancy
• Pregnant or lactating women.
• History of infusion reactions to bevacizumab or other monoclonal antibody therapies.
• Inadequately controlled hypertension with or without current antihypertensive medications

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Klatskin Tumor

Interventions

Optical Imaging

Condition Hierarchy (Ancestors)

Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• G. M. van Dam, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• M. T. de Boer, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• W. B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

W B Nagengast, MD, PhD, PharmD

CONTACT

+31503612620; w.b.nagengast@umcg.nl

A B de Vries, MD

CONTACT

+31503612586; a.b.de.vries01@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. W.B. Nagengast, Gastroenterologist, Principal Investigator

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: August 8, 2018
• Study Start: April 1, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)