PRIMARY OBJECTIVE:~• To determine the recommended phase II dose (RP2D) of NBTXR3 activated by radiotherapy in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma.~SECONDARY OBJECTIVES:~To evaluate the safety and feasibility of NBTXR3 intratumoral injection activated by radiotherapy in locally advanced or borderline-resectable pancreatic ductal adenocarcinoma~To evaluate the anti-tumor response of NBTXR3 intratumoral injection activated by radiotherapy in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma~To evaluate time-to-event outcomes in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma~EXPLORATORY OBJECTIVES:~To evaluate the body kinetic profile of intratumorally injected NBTXR3.~To evaluate time to event outcomes for subjects with clinical staging of locally advanced, unresectable disease.~To evaluate resectability conversion rates.~To evaluate surgical outcomes in subjects who undergo surgery after radiation therapy.~To associate radiomic measurements with outcomes.~To evaluate biomarkers of response in subjects treated with NBTXR3/RT.~OUTLINE: This is a dose-escalation study of NBTXR3.~Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo 15 fractions of intensity modulated radiation therapy (IMRT) between days 15-43 in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.
To find the recommended dose of NBTXR3 that can be given in combination with radiation therapy to patients with pancreatic cancer. To learn if the dose NBTXR3 found in Part 1 can help to control the disease.