Clinical Trials /

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

NCT04207944

Description:

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 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 (pancreas protocol CT or CT angiogram of the pancreas) 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.

Related Conditions:
  • Pancreatic Intraductal Papillary-Mucinous Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04207944

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: Pro00103684
  • SECONDARY ID: 1R01CA235677-01A1
  • NCT ID: NCT04207944

Conditions

  • IPMN
  • IPMN, Pancreatic

Interventions

DrugSynonymsArms
Sulindac 400 MGSulindac

Purpose

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 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 (pancreas protocol CT or CT angiogram of the pancreas) 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 a pancreas CT or CT
      angiogram of the pancreas 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 BID for 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. Pancreatic CT will be performed 1 year after randomization (+/- 4
      weeks) and then annually. The intent of these timings is to have the EUS and CT 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. 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 200 patients during a period of 2 years and will follow all
      patients for 3 additional years, for a total trial duration of 5 years.

Trial Arms

NameTypeDescriptionInterventions
SulindacExperimentalPatients 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.
  • Sulindac 400 MG
PlaceboPlacebo ComparatorPatients will be randomized to receive standard radiographic/endoscopic surveillance plus placebo. Patients will continue placebo for 3 years during follow-up.

    Eligibility Criteria

            Inclusion Criteria:

          1. Subject is a man or woman between the ages of 21 and 85 years.

          2. Subject has high-risk IPMN as defined below.

               1. Patient has undergone partial pancreatectomy for non-invasive IPMN AND has
                  residual cyst(s) > 1 cm

               2. Patient has a radiographic lesion of the pancreas consistent with IPMN as
                  documented by:

             i. Cyst fluid CEA > 192 ng/ml OR MRI confirmation of communication with main
             pancreatic duct AND has any of the following worrisome features:

               -  Cyst > 3 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 cancer.

          2. Subject takes an NSAID 3 or more times per week.

          3. Subject has a history of or currently has known allergy to NSAIDs or a
             contraindication to use of NSAIDs in the opinion of the treating investigator.

          4. Subject has a history of gastric ulcer, non-iatrogenic intestinal perforation,
             gastrointestinal bleeding from NSAID use for which intervention was required, renal
             insufficiency (eGFR <60 mL/minute/1.73 m2), venous thromboembolism, cirrhosis, asthma,
             or any other condition that serves as a contraindication to the use of sulindac.

          5. Myocardial infarction or coronary artery bypass grafting within six months of study
             entry.

          6. Congestive Heart Failure.

          7. Severe adverse drug reaction to iodinated contrast agents that cannot be managed with
             routine premedication prior to imaging.

          8. Prior diagnosis or active treatment for (other) prior malignancy (except in situ
             cancers) within the previous 3 years.

          9. History of medical procedure that would prevent an endoscopic ultrasound from being
             performed (such as gastric bypass, prior total gastrectomy).

         10. Subject is lactating or pregnant.
    Maximum Eligible Age:85 Years
    Minimum Eligible Age:21 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Percent of patients with IPMN progression as measured by a composite of several indicators
    Time Frame:3 years
    Safety Issue:
    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 ≥5 mm Increase in diameter of the main pancreatic duct by >3mm Pancreatic resection The development of an invasive cancer.

    Secondary Outcome Measures

    Measure:Percent of patients with cyst progression as measured by radiographic images
    Time Frame:3 years
    Safety Issue:
    Description:1. All initial and follow-up CT 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.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Duke University

    Last Updated

    March 30, 2021