Intraoperative Near-infrared Fluorescence Imaging in Pancreatic- and Extrahepatic Bile Duct Tumors Using cRGD-ZW800-1 and Dedicated Imaging Systems: A Phase II Feasibility Testing, Dose-ranging and Optimal Dose-(Interval) Selection Trial

Pancreatic cancer is one of the most common causes of death in the United States. With a median survival of less than 6 months, the prognosis is very poor. After diagnosis, the 1 and 5-year survival rates are around 25% and 10%, respectively. Surgical resection is the only curative treatment, but also results in relatively low survival and present recurrence risk, depending on the stage. In the same order of magnitude, bile duct cancer is also found, it can be classified according to location within or outside the liver, extrahepatic bile duct tumors are much anatomically related to pancreatic tumors, surgical treatment is therefore often the same: (partial) pancreatic resection. During surgery, it is difficult to distinguish between malignant and benign tissue, especially if patients have been treated neoadjuvantly. Currently, near-infrared fluorescence imaging is a technique with great potential to illuminate important structures during surgery. Fluorescent substances can be injected intravenously, which then specifically attach to malignant cells or tumor-associated structures, such as stroma or blood vessels, and emit light in the near-infrared spectrum (700-900 nm). Thus, with specially equipped camera systems, tumors literally light up and the surgeon can completely remove the tumors during surgery in real time. cRGD-ZW800-1 is a newly developed fluorescent agent, which binds to integrins, which are associated with neoangiogenesis, and has the potential to make tumor cells in the pancreas more visible during surgery in order to achieve more complete surgical (R0) resections.

Aims of the study:

• To assess the feasibility, safety and tolerability of cRGD-ZW800-1 for the visualization of pancreatic carcinomas, perihilar or distal cholangiocarcinomas and if present associated metastatic lymph nodes and their distant metastases in real-time using specific NIR fluorescence imaging systems.
• Determining the optimal dose and dose interval of a single intravenous bolus injection of cRGD-ZW800-1 for intraoperative NIR imaging

Study design:

Open label, dose-ranging and optimal dose-(interval) selection study, with a two-factorial design. In total 20 patients diagnosed with a malignant tumor of the pancreas, or distal/hilar bile ducts, which are eligible for surgical resection with or without neoadjuvant treatment will be enrolled. These patients will be distributed over four dosing-, and one expansion cohort: Cohort 1 (0.05mg/kg, 2-4h before intervention), Cohort 2 (0.05mg/kg, 14-24h before intervention), Cohort 3 (0.025mg/kg, 2-4h before intervention), Cohort 4 (0.025mg/kg, 14-24h before intervention) and Cohort 5 (expansion cohort). Patients are included if they met the inclusion/exclusion criteria and will be screened during pre-operative work-up for surgery.