The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)

This is a multi-center randomized double-blind placebo controlled trial of patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The primary objective is to evaluate the effect of sulindac on the presence or absence of progression of IPMN after up to 3 years of treatment. Patients without contraindications will be considered to be eligible and will be required to have a cross-sectional imaging study of the pancreas by CT scan or MRI within 3 months of study entry to document residual IPMNs and to rule out any evidence of pancreatic cancer. Patients will be randomized to receive either sulindac (200 mg p.o. BID) plus standard radiographic and endoscopic surveillance or placebo plus standard radiographic and endoscopic surveillance. Randomization will be stratified by (1) whether the patient had high-grade dysplasia identified in the initial resection specimen (resected patients only) and (2) whether the patient is taking metformin at the time of randomization.

Inclusion Criteria: 1. Subject is a man or woman between the ages of 21 and 85 (inclusive) years. 2. Subject has high-risk IPMN as defined below. 1. Patient (previously resected) has undergone partial pancreatectomy for non-invasive IPMN AND has new or residual cyst(s) \> 1 cm and/or 2. Patient (not previously resected) has a radiographic lesion of the pancreas consistent with IPMN as documented by: Cyst fluid CEA \> 192 ng/ml OR presence of GNAS or RNF 43 mutation noted in cyst fluid OR MRI imaging confirmation of "likely", "probable" or "confirmed" communication with main pancreatic duct AND at least one of the following worrisome features: * Cyst \> 2.5 cm * Thickened/enhancing cyst walls * Main pancreatic duct \> 5mm * Abrupt change in caliber of pancreatic duct with distal atrophy 3. Subjects has ECOG of 0-2 4. Subject is medically fit to undergo EUS. 5. Female subjects who are of childbearing potential or are capable of becoming pregnant must be willing to use appropriate methods of contraception for the length of the study. 6. Subject is able to provide written informed consent. Exclusion Criteria: 1. Subject has pathologic evidence of pancreatic adenocarcinoma. 2. Subject takes a systemic corticosteroid or NSAID more than 3 times per week. 3. Subject has a known history of or currently existing allergy to NSAIDs, aspirin induced asthma, gastric ulcers, non-iatrogenic intestinal perforation, or gastrointestinal bleeding from NSAID usage for which intervention was required.. 4. Subject has an ongoing history of renal insufficiency (eGFR \