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

Primary Purpose

IPMN, IPMN, Pancreatic

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sulindac 400 MG
Placebo
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for IPMN

Eligibility Criteria

21 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 Patient (not previously resected) has a radiographic lesion of the pancreas consistent with IPMN as documented by:
    2. Cyst fluid CEA > 192 ng/ml OR presence of GNAS or RNF 43 mutation noted in cyst fluid OR MRI imaging confirmation of 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 NSAID or corticosteroid 3 or more 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 <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.
  5. Myocardial infarction or coronary artery bypass grafting within six months of study entry.
  6. Diagnosis of Congestive Heart Failure.
  7. Severe adverse drug reaction to iodinated contrast agents that cannot be managed with routine premedication prior to imaging.
  8. Diagnosis for (other) prior malignancy (except in situ and non-melanoma skin cancers) within the previous 3 years and actively receiving antineoplastic or immuno therapy within 90 days of randomization.
  9. History of medical procedure that would prevent an endoscopic ultrasound from being performed (such as Roux-en-Y, prior total gastrectomy).
  10. Subject is lactating or pregnant.

Sites / Locations

  • Johns Hopkins UniversityRecruiting
  • Massachusetts General HospitalRecruiting
  • Memorial Sloan KetteringRecruiting
  • Duke University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sulindac

Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

Percent of patients with IPMN progression as measured by a composite of several indicators
Patients will be determined to have progressed if they have: New cystic lesion(s) of the pancreas >1 cm in diameter (or initial lesion(s) <5 mm that are now >1cm), Doubling of the diameter of any preexisting cyst initially measuring β‰₯5 mm Increase in diameter of the main pancreatic duct by >3mm Pancreatic resection The development of pancreatic adenocarcinoma

Secondary Outcome Measures

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

Full Information

First Posted
December 19, 2019
Last Updated
July 12, 2023
Sponsor
Duke University
Collaborators
Johns Hopkins University, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04207944
Brief Title
The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)
Official Title
Preventing an Incurable Disease: The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2020 (Actual)
Primary Completion Date
August 31, 2027 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Johns Hopkins University, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IPMN, IPMN, Pancreatic

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sulindac
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will be randomized to receive standard radiographic/endoscopic surveillance plus placebo. Patients will continue placebo for 3 years during follow-up.
Intervention Type
Drug
Intervention Name(s)
Sulindac 400 MG
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent of patients with IPMN progression as measured by a composite of several indicators
Description
Patients will be determined to have progressed if they have: New cystic lesion(s) of the pancreas >1 cm in diameter (or initial lesion(s) <5 mm that are now >1cm), Doubling of the diameter of any preexisting cyst initially measuring β‰₯5 mm Increase in diameter of the main pancreatic duct by >3mm Pancreatic resection The development of pancreatic adenocarcinoma
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Percent of patients with cyst progression as measured by radiographic images
Description
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.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Percent of patients with Inflammatory Marker Progression
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Allen, MD
Phone
919-684-6858
Email
peter.allen@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Elizabeth Bronson
Phone
919-668-2382
Email
elizabeth.bronson@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Allen, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin He, MD
Phone
410-614-7551
Email
jhe11@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Sherry Leung
Email
sleung7@jhu.edu
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos Fernandez, MD
Phone
617-726-5644
Email
cfernandez@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Amarachi Ike
Email
aike@mgh.harvard.edu
Facility Name
Memorial Sloan Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Soares, MD
Phone
212-639-3195
Email
soaresk@mskcc.org
First Name & Middle Initial & Last Name & Degree
Nan Pang
Email
pangn@mskcc.org
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Bronson
Phone
919-668-2328
Email
elizabeth.bronson@duke.edu
First Name & Middle Initial & Last Name & Degree
Stacy Murray
Phone
919-684-7983
Email
stacy.murray@duke.edu
First Name & Middle Initial & Last Name & Degree
Peter Allen, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data will only be shared through publication.

Learn more about this trial

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

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