Fluorescence Image Guided Surgery in Cholangiocarcinoma (COUGAR)
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|ClinicalTrials.gov Identifier: NCT03620292|
Recruitment Status : Not yet recruiting
First Posted : August 8, 2018
Last Update Posted : August 15, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Hilar Cholangiocarcinoma||Drug: Bevacizumab-IRDye800CW Device: near infrared (NIR) fluorescence imaging||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Cholangiocarcinoma Detection Using an Intraoperative Fluorescence Image Guided Approach With Bevacizumab-IRDye 800CW|
|Estimated Study Start Date :||August 10, 2018|
|Estimated Primary Completion Date :||January 1, 2020|
|Estimated Study Completion Date :||January 1, 2020|
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
Intravenous administration of Bevacizumab-IRDye800CW prior to surgery for hilar cholangiocarcinoma
Other Name: Tracer administration
Device: near infrared (NIR) fluorescence imaging
Intraoperative NIR fluorescence imaging of hilar cholangiocarcinoma, lymph nodes, resection margins, resection specimens
Other Name: optical imaging
- Optimal dose finding of Bevacizumab 800CW in hilar cholangiocarcinoma [ Time Frame: 24 months ]- 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).
- Peroperative detection of hilar cholangiocarcinoma with real-time near-infrared fluorescence camera [ Time Frame: 24 months ]- Comparison between perioperative fluorescent imaging and ex vivo analysis (histology, breadloaf slices) to see if detection of tumor tissue is feasible. I.e. is high fluorescent signal corresponding with localization of tumor tissue in ex-vivo analysis?
- Detection of hilar cholangiocarcinoma in real-time near-infrared fluorescence ex-vivo endoscopy [ Time Frame: 24 months ]- Comparison of endoscopic fluorescent imaging and ex vivo analysis(histology, breadloaf slices) to see if endoscopic detection is feasible. I.e. is high fluorescent signal seen during ex-vivo endoscopy corresponding with localization of tumor tissue in ex-vivo analysis?
- Establish tracer distribution in tumour tissue [ Time Frame: 24 months ]- Visualisation of tracer distribution at microscopic level using ex vivo needle based confocal laser endomicroscopy.
- Measurement of fluorescence in tumour tissue en surrounding normal tissue [ Time Frame: 24 months ]- Correction for scattering and measurement of fluorescent signal using spectroscopy ex vivo.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03620292
|Contact: W B Nagengast, MD, PhD, PharmDfirstname.lastname@example.org|
|Contact: A B de Vries, MDemail@example.com|
|University Medical Center Groningen||Not yet recruiting|
|Groningen, Netherlands, 9713 GZ|
|Contact: W. B. Nagengast, MD, PhD, PharmD +31503612620 firstname.lastname@example.org|
|Contact: A. B. de Vries, MD +31503612586 email@example.com|
|Principal Investigator: W. B. Nagengast, MD, PhD, PharmD|
|Principal Investigator: G. M. van Dam, MD, PhD|
|Principal Investigator: M. T. de Boer, MD,PhD|
|Principal Investigator:||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|