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 2 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:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)
  • Official Title: 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 200 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 2 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) 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. A standard of care for
      this group of patients is obtaining a CT every 6-12 months. Rather than repeating a CT
      earlier, we would simply wait to enroll (and approach) patients at the time of their
      regularly scheduled CT.

      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, HbA1c, CA19-9 and CEA. 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. Patients will be evaluated annually for the primary endpoint. Adjustments of
      study drug dosing will be made as needed.

      We 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 200 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:
    
              -  Subject is a man or woman between the ages of 21 and 85 years.
    
              -  Subject has high-risk IPMN as defined above.
    
              -  Subjects has ECOG of 0-2
    
              -  Subject is medically fit to undergo EUS.
    
              -  Subject is able to provide written informed consent.
    
              -  Female subjects who are of childbearing potential must be willing to use appropriate
                 methods of contraception for the length of the study.
    
            Exclusion Criteria:
    
              -  Subject has pathologic evidence of pancreatic cancer.
    
              -  Subject takes an NSAID as a daily medication.
    
              -  Subject has a history of or currently has known allergy to NSAIDs
    
              -  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.
    
              -  Myocardial infarction or coronary artery bypass grafting within six months of study
                 entry.
    
              -  Congestive Heart Failure.
    
              -  Severe adverse drug reaction to iodinated contrast agents that cannot be managed with
                 routine premedication prior to imaging.
    
              -  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, we will further explore the set of 256 imaging features that broadly describe variation in radiographic enhancement patterns (i.e. heterogeneity). Using image analysis techniques, we will derive quantitative measurements of the cyst wall and will determine the presence and degree of solid enhancing component suggestive of malignancy.
    Measure:Percent of patients with Inflammatory Marker Progression
    Time Frame:3 years
    Safety Issue:
    Description:2. Cyst fluid obtained at the time of annual EUS 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.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Duke University

    Last Updated

    December 19, 2019