NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer

Inclusion Criteria: 1\. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study 2. Age ≥ 18 years 3. Biopsy proven ductal adenocarcinoma of the pancreas,as defined by the following: a. Borderline resectable pancreatic adenocarcinoma (BRPC) has no aortic involvement with at least ONE of the following features: i. Superior mesenteric vein (SMV) or Portal vein (PV) with a tumor interface of ≥ 180° OR short segment occlusion of SMV or PV amenable to reconstruction ii. Superior mesenteric artery (SMA) or celiac axis (CA) with a tumor interface of \< 180° iii. Any degree of hepatic artery interface that is amenable to reconstruction b. Locally advanced pancreatic adenocarcinoma (LAPC) has at least ONE of the following features: 1. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study 2. Age ≥ 18 years 3. Biopsy proven ductal adenocarcinoma of the pancreas,as defined by the following: a. Borderline resectable pancreatic adenocarcinoma (BRPC) has no aortic involvement with at least ONE of the following features: i. Superior mesenteric vein (SMV) or Portal vein (PV) with a tumor interface of ≥ 180° OR short segment occlusion of SMV or PV amenable to reconstruction ii. Superior mesenteric artery (SMA) or celiac axis (CA) with a tumor interface of \< 180° iii. Any degree of hepatic artery interface that is amenable to reconstruction b. Locally advanced pancreatic adenocarcinoma (LAPC) has at least ONE of the following features: i. Occlusion of the SMV or PV that is not amenable to reconstruction ii. Tumor interface of the superior mesenteric artery or celiac axis ≥ 180° iii. Involvement of the hepatic artery that is not amenable to reconstruction iv. Involvement of the aorta 4. Has had a 4-month course (± 2-months) of chemotherapy for PDAC without radiographic evidence of distant metastatic disease. Following chemotherapy regimens are allowed: 1. gemcitabine/nab-paclitaxel 2. gemcitabine/capecitabine 3. gemcitabine/cisplatin 4. gemcitabine 5. FOLFOX 6. FOLFIRINOX 5. Amenable to undergo the endoscopic ultrasound guided injection of NBTXR3 as per investigator or treating physician. 6. Has a target lesion in the pancreas that is identifiable on cross sectional imaging by repeated measurements (via RECIST 1.1) at the same anatomical location a. Nodal disease only is not allowed. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 8. Laboratory Values at screening: 1. Hemoglobin ≥ 8.0 g/dL 2. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 3. Platelet Count ≥ 100,000/mm3 4. Creatinine ≤ 1.5 x upper limit of normal (ULN) 5. Total Bilirubin ≤ 2.0 mg/dL 6. AST / ALT ≤ 3.0 x upper limit of normal (ULN) 7. Serum albumin ≥ 3.0 g/dL 9. Negative pregnancy test ≤ 7 days prior to NBTXR3 injection in all females of child-bearing potential 10. If participant has a history of prior duodenal or biliar plastic stent, it should be replaced with a metal stent ≥ 1 week prior to Study Day 1. Exclusion Criteria: 1. Prior radiation therapy to the upper abdomen 2. Prior surgical resection of pancreatic tumor 3. Diagnosis other than pancreatic ductal adenocarcinoma. All other histologic types (i.e., adenosquamous, cystadenocarcinoma, etc.) are not eligible to participate on this study. 4. LAPC or BRPC with radiographic evidence of distant metastasis at screening. 5. Has received any approved or investigational anti-neoplastic agent other than the chemotherapies specified in this protocol (i.e. chemotherapies included in Inclusion #4) 6. Known uncontrolled (Grade ≥ 2) or active gastric or duodenal ulcer disease within 30 days of enrollment 7. Known contraindication to iodine-based or gadolinium-based IV contrast 8. Active malignancy, in addition to pancreatic cancer, with the exception of basal cell carcinoma of the skin definitively treated and relapse free within at least 1 year from diagnosis 9. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second or third degree atrioventricular heart block without a permanent pacemaker in place) 10. Class III or IV Congestive Heart Failure as defined by the New York Heart Association functional classification system \<6 months prior to screening 11. Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C infection a. Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible. 12. Female patients who are pregnant or breastfeeding 13. Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control for the entire study period. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of \< 1% per year when used consistently and correctly 14. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments