Near-infrared Image Guided Surgery in Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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There is a need for better visualization of resection margins and detection of small tumor deposits during surgery for pancreatic cancer. Optical molecular imaging of pancreatic ductal adenocarcinoma associated biomarkers is a promising technique to accommodate this need. The biomarker Vascular Endothelial Growth Factor (VEGF-A) is overexpressed in pancreatic cancer tissue versus normal tissue and has proven to be a valid target for molecular imaging. VEGF-A can be targeted by the monoclonal antibody bevacizumab. Monoclonal antibodies can be labeled by the near-infrared (NIR) fluorescent dye IRDye800CW (800CW). The investigators hypothesize that bevacizumab-800CW accumulates in VEGF expressing cancer, enabling pancreatic cancer visualization using a NIR intraoperative camera system. In this pilot intervention study the investigators will determine the optimal dosage of bevacizumab-800CW (4,5 10, 25 or 50mg) to detect pancreatic cancer tissue intraoperatively.

Official Title
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Intraoperative Detection of Cancer Tissue in Pancreatic Adenocarcinoma Using a VEGF-targeted Optical Fluorescent Imaging Tracer, A Multicentre Feasibility Dose Escalation Study

Conditions
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Pancreatic Cancer, Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Bevacizumab-800CW


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Patients with clinical suspicion of pancreatic head cancer who are scheduled to undergo surgical intervention with curative intent World Health Organization (WHO) performance score 0-2. Signed written informed consent Exclusion Criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent. Other invasive malignancy Pregnant or lactating women. Documentation of a negative pregnancy test must be available for woman of childbearing potential. Woman of childbearing potential are pre- menopausal women with intact reproductive organs and women less than two years after menopause. Prior neo-adjuvant chemo- of radiotherapy 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, Transient Ischemic Attack, Cerebral Vascular Accident, pulmonary embolism, uncontrolled chronic hepatic failure, unstable angina pectoris. Anticoagulant therapy with vitamine K antagonists Patients receiving Class 1A (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents Evidence of QTc (corrected QT interval) prolongation on pretreatment ECG (greater than 44ms in males of greater than 450ms in females) Magnesium, potassium and calcium below the lower limit of normal range.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: phase I/II safety and dose-finding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Bevacizumab-800CW | Drug: Bevacizumab-800CW<br>* dose finding: 4.5mg; 10mg; 25mg; 50mg<br>* Other names: Bevacizumab-IRDye800CW;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tracer accumulation in tumor tissue vs normal pancreatic tissue assessed by intraoperatively and ex vivo measuring of the mean fluorescent intensity | Mean Fluorescent Intensity (MFI) measured in tumor tissue compared to normal pancreatic tissue at macroscopic and microscopic level | up to 6 months | 
| Finding optimal dose of Bevacizumab-800CW for intraoperative imaging of pancreatic cancer measured by calculating Target to Background ratios (TBR) | TBR of each dose group assessed by intraoperative imaging as well as ex vivo imaging | 3 days after tracer injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events |  | Up to 4 weeks after tracer injection |