Neoplasms

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Pancreatic Neoplasms

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Pancreatic Intraductal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

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Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Hypoglycemic Agents

All Drugs and Chemicals

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Antirheumatic Agents

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Metformin

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus sulindac. The sulindac starting dose is 200 mg by mouth 2x daily. Patients will continue drug for 3 years during follow-up.

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus placebo. Patients will continue placebo for 3 years during follow-up.

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus sulindac. The sulindac starting dose is 200 mg by mouth 2x daily. Randomization will be performed at Duke and stratified by (1) the presence of high-grade dysplasia on the operative pathologic report and (2) the use of metformin at the time of enrollment. Patients will be provided the study drugs by a Duke, MSK, MGH, or JHH pharmacist. Patients will continue drug/placebo for 3 years during follow-up.

Sulindac 400 MG

Placebo

Peter Allen, MD

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.

This is a phase 2 multicenter, randomized, double-blind, placebo-controlled clinical trial of patients who have high-risk intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Patients will be randomized in a 1:1 fashion and stratified by whether the patient had high-grade dysplasia (yes vs. no vs. no resection) identified in the initial resection specimen (for resected subjects), and whether or not the patient is taking metformin at the time of randomization. Patients will be required to have undergone an MRI or CT angiogram for IPMN active surveillance in accordance with the standard practice at the enrolling institution within 3 months of study entry. The CT imaging study will be used to document baseline IPMN characteristics and to ensure that there is no evidence of a preexisting pancreatic cancer.

Following randomization, patients will take the study drug or placebo twice daily for up to 3 years. Both the study drug arm and the placebo arm will undergo standard laboratory, radiographic, and endoscopic assessment for IPMN progression. Every 6 months, patients will undergo assessment of serum CMP, CBC, and CA19-9. EUS will be performed 6 months after randomization (+/- 4 weeks) and then annually. CT or MRI will be performed 1 year after randomization (+/- 4 weeks) and then annually. The intent of these timings is to have the EUS and CT/MRI be on an alternating 6-month schedule per standard of care.

Patients, nurses, and physicians will be blinded to the randomization. Study drug will be provided to patients in the outpatient clinic or mailed to their home. Pill diaries will be provided at the time that the study drugs are given and will be evaluated every 6 months, at the time of routine follow-up.

Safety and efficacy will be assessed throughout the treatment period. Assessment for study drug complications will be made by phone call every other month (in between routine follow-up) and at routine follow-up every 6 months by the attending surgeon or designee, until the end of the study. If a complication is identified, the study drug will be discontinued. Patient evaluations will be scheduled bi-annually for the primary endpoint and off-schedule evaluations may be made to address symptoms or clinical concerns as they arise.

The investigators plan to accrue 100 patients and will follow all patients for up to 3 additional years until protocol defined progression or study closure, whichever occurs first.

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

Preventing an Incurable Disease: The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)

Data will only be shared through publication.

2. Cyst fluid obtained at the time of annual EUS or surgical resection will be used to determine whether cyst fluid inflammatory marker analysis can identify progression. Antibody bead array analysis will be used to assess whether previously developed biomarker models for high-risk IPMN (IL-4/sFASL and MMP-9/CA72-4) can identify patients with an increased risk of radiographic progression. Archival tissue will be collected to validate cyst fluid analysis.

Patients will be determined to have progressed if they have:

1. New cystic lesion(s) of the pancreas \>1 cm in diameter (or initial lesion(s) \<5 mm that are now \>1cm),
2. Doubling of the diameter of any preexisting cyst initially measuring ≥5 mm
3. Increase in diameter of the main pancreatic duct by \>3mm
4. Pancreatic resection
5. The development of pancreatic adenocarcinoma

1. All initial and follow-up radiographic imaging will be quantitatively assessed for radiographic changes associated with progression. Utilizing a recently described radiomics approach to the evaluation of imaging in patients with IPMN, the investigators will further explore the set of 256 imaging features that broadly describe variation in radiographic enhancement patterns (i.e. heterogeneity). Using image analysis techniques, the investigators will derive quantitative measurements of the cyst wall and will determine the presence and degree of solid enhancing component suggestive of malignancy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)	NCT04207944	IPMN IPMN, Pancreati...	Sulindac 400 MG Placebo	21 Years - 85 Years	Duke University
The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)	NCT04207944	IPMN IPMN, Pancreati...	Sulindac 400 MG Placebo	21 Years - 85 Years	Duke University

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