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

NCT04207944 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: Pro001036841R01CA235677-01A1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

IPMN; IPMN, Pancreatic

Outcome Measures

Primary Outcomes (1)

• Percent of patients with IPMN progression as measured by a composite of several indicators

  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

  3 years

Secondary Outcomes (1)

• Percent of patients with cyst progression as measured by radiographic images

  3 years

Other Outcomes (1)

• Percent of patients with Inflammatory Marker Progression

  3 years

Study Arms (2)

Sulindac

EXPERIMENTAL

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.

Drug: Sulindac 400 MG

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Sulindac 400 MG DRUG

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

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is a man or woman between the ages of 21 and 85 (inclusive) years.
• Subject has high-risk IPMN as defined below.
• Patient (previously resected) has undergone partial pancreatectomy for non-invasive IPMN AND has new or residual cyst(s) \> 1 cm and/or
• 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
• Subjects has ECOG of 0-2
• Subject is medically fit to undergo EUS.
• 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.
• Subject is able to provide written informed consent.

You may not qualify if:

• Subject has pathologic evidence of pancreatic adenocarcinoma.
• Subject takes a systemic corticosteroid or NSAID more than 3 times per week.
• 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..
• Subject has an ongoing history of renal insufficiency (eGFR \<50 mL/minute/1.73 m2), cardiovascular disease, gastrointestinal disorder, or any other condition that serves as a contraindication to the use of sulindac in the opinion of the treating investigator.
• Myocardial infarction or coronary artery bypass grafting within six months of study entry.
• Diagnosis of Congestive Heart Failure.
• Severe adverse drug reaction to contrast agents that cannot be managed with routine premedication prior to imaging.
• Diagnosis for (other) prior malignancy (except in situ and non-melanoma skin cancers) and are actively receiving antineoplastic or immuno therapy within 90 days of randomization.
• History of medical procedure that would prevent an endoscopic ultrasound from being performed (such as Roux-en-Y, prior total gastrectomy).
• Subject is lactating or pregnant.

Sponsors & Collaborators

• Duke University: lead
• Johns Hopkins University: collaborator
• Massachusetts General Hospital: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering

New York, New York, 10021, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Pancreatic Intraductal Neoplasms

Interventions

Sulindac

Condition Hierarchy (Ancestors)

Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Peter Allen, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: July 10, 2020
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)