Clinical trial NCT03620292: Fluorescence Image Guided Surgery in Cholangiocarcinoma
Official title: Cholangiocarcinoma Detection Using an Intraoperative Fluorescence Image Guided Approach With Bevacizumab-IRDye 800CW
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hilar Cholangiocarcinoma
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2018-08-08
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

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.

Primary outcomes:
measure: Optimal dose finding of Bevacizumab 800CW in hilar cholangiocarcinoma
timeFrame: 24 months
Secondary outcomes:
measure: Peroperative detection of hilar cholangiocarcinoma with real-time near-infrared fluorescence camera
timeFrame: 24 months
measure: Detection of hilar cholangiocarcinoma in real-time near-infrared fluorescence ex-vivo endoscopy
timeFrame: 24 months
measure: Establish tracer distribution in tumour tissue
timeFrame: 24 months
measure: Measurement of fluorescence in tumour tissue en surrounding normal tissue
timeFrame: 24 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: G. M. van Dam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: M. T. de Boer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: W. B. Nagengast, MD, PhD, PharmD
role: PRINCIPAL_INVESTIGATOR
References: