Fluorescence Image Guided Surgery in Cholangiocarcinoma

NCT ID: NCT03620292

Last Updated: 2021-04-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2021-12-01

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.

Detailed Description

See brief summary

Conditions

Hilar Cholangiocarcinoma

Study Design

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

Study Groups

Intraoperative NIR fluorescence imaging

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

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

near infrared (NIR) fluorescence imaging

Intervention Type: DEVICE

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

Interventions

Bevacizumab-IRDye800CW

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

Intervention Type: DRUG

near infrared (NIR) fluorescence imaging

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

Intervention Type: DEVICE

Other Intervention Names

Tracer administration; optical imaging

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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
• Within 6 months prior to inclusion: myocardial infarction, TIA, CVA pulmonary embolism, uncontrolled chronic hepatic failure, unstable angina pectoris.

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

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

dr. W.B. Nagengast, MD

Dr. W.B. Nagengast, Gastroenterologist, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

G. M. van Dam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

M. T. de Boer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

W. B. Nagengast, MD, PhD, PharmD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

W B Nagengast, MD, PhD, PharmD

Role: CONTACT

w.b.nagengast@umcg.nl

+31503612620

A B de Vries, MD

Role: CONTACT

a.b.de.vries01@umcg.nl

+31503612586

Facility Contacts

W. B. Nagengast, MD, PhD, PharmD

Role: primary

w.b.nagengast@umcg.nl

+31503612620

A. B. de Vries, MD

Role: backup

a.b.de.vries01@umcg.nl

+31503612586

Other Identifiers

NL65378.042.18

Identifier Type: -

Identifier Source: org_study_id