Adenocarcinoma of the Pancreas

Prospective multicenter study in which all patients with borderline or locally advanced pancreatic adenocarcioma undergoing neoadjuvant chemotherapy and surgical exploration with curative intent will be included for one year. Preoperative images by traditional CT and 3D-MSP technology will be evaluated, comparing the accuracy variables (sensitivity, specificity, predictive values, area under the curve, concordance index) of both techniques with the gold standard (results of surgery and histopathological analysis).

The purpose of this trial is to evaluate the safety of the HistoSonics Edison System for the destruction of pancreatic adenocarcinomas using histotripsy.

This will be a phase I/II trial examining the safety and tolerability of pre-operative mFOLFIRINOX in combination with peri-operative oral hydroxychloroquine (FHQ) in the treatment of subjects with adenocarcinoma of the pancreas. Subjects will be staged prior to protocol entry by contrast-enhanced helical abdominal CT scan done using a pancreas mass protocol or EUS. Eligible subjects with biopsy-proven, resectable pancreatic adenocarcinoma without evidence of venous or arterial involvement on CT scan receive HCQ orally in combination with mFOLFIRINOX prior to surgery. Hydroxychloroquine will begin with the first dose of mFOLFIRINOX and continue for 2 weeks post-operatively. Three to six weeks after the last dose of mFOLFIRINOX, patients will undergo surgical exploration and pancreatectomy if technically feasible and all toxicities have resolved. Pathologic specimens will undergo detailed histopathologic and immunohistochemical evaluations with particular attention to the six surgical margins of resection: the bile duct margin (for Whipple specimens), the margin of pancreatic transection, the retroperitoneal margin, the proximal and distal duodenal margins (for Whipple specimens), and the portal vein margin along the pancreatic head (for Whipple specimens) or medial pancreas (for distal pancreatectomies). Tissue specimens will be stored at -80C for future correlative studies of autophagy and tumor response to protocol therapy. Ten to fourteen weeks following completion of successful surgical removal of their tumor, subjects will undergo repeat staging studies per standard of care. Subjects will pursue standard of care adjuvant therapy options at the discretion of their physician.

This is a clinical trial that tests a surgical treatment. Everyone in the study will get the same treatment, and there is no comparison or placebo group. Patients can join the study if they have pancreatic cancer that has spread to only a few spots in the liver or lungs. They must be receiving a type of chemotherapy called NALIRIFOX before surgery (this is called neoadjuvant chemotherapy). If the cancer gets worse during or after the first 4 cycles of chemotherapy, the patient will be removed from the study. If the cancer stays the same or gets smaller after the first 4 cycles, doctors will check if the main tumor can be removed with surgery. If the tumor cannot be removed, the patient will get 4 more cycles of chemotherapy as standard of care. If the main tumor can be removed, the patient will have surgery 2-6 weeks after finishing chemotherapy. During surgery, doctors will try to remove both the main tumor and the small tumors in the liver or lungs. If, during surgery, the doctor finds that the main tumor actually cannot be removed, the patient may receive 4 more cycles of chemotherapy starting 2-4 weeks after surgery.

This is a proof-of-concept, Open label, randomized, multicentric, superiority phase-2 study.

Curative management of locally resectable invasive adenocarcinomas located in the cephalic region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major surgery that often leads to major complications including approximately 20% of relevant clinical postoperative pancreatic fistula. Postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy, i.e., chemotherapy for malignancy is performed in only about a third of patients who experienced a grade C fistula. A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that involves the complete and definitive resection of all pancreatic tissue, eliminating any risk of postoperative pancreatic fistula but is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes". Total Pancreatectomy following by intraportal Islet AutoTransplantation (TPIAT) can prevent "brittle diabetes" and improve the quality of life. The endocrine islets can be isolated from the pancreatic surgical specimen with standardized procedures and transplanted in the liver through intraportal infusion, in absence of immunosuppression and allow adequate control of glucose metabolism with a reduced need for exogenous insulin and an effective graft function in 70% of cases at 3 years Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy, while maintaining an adequate metabolic control.