Fluorescence Image Guided Surgery in Cholangiocarcinoma

Sponsor
University Medical Center Groningen
Study ID
NCT03620292
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

  • Hilar Cholangiocarcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab-IRDye800CW — DRUG
    Intravenous administration of Bevacizumab-IRDye800CW prior to surgery for hilar cholangiocarcinoma
  • near infrared (NIR) fluorescence imaging — DEVICE
    Intraoperative NIR fluorescence imaging of hilar cholangiocarcinoma, lymph nodes, resection margins, resection specimens

Study Details

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.

Key Dates

First listed
Aug 8, 2018
Start date
Apr 1, 2019
Status verified
Apr 2021
Primary completion
Dec 1, 2021
Completion
Dec 1, 2021

Study Design

Enrollment
12 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC

Arms

  • Experimental: 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

Primary Outcome Measure

Optimal dose finding of Bevacizumab 800CW in hilar cholangiocarcinoma [ Time Frame: 24 months ]

Central Contacts