Comparing the Clinical Impact of Pancreatic Cyst Surveillance Programs and Associated Biomarkers

PRIMARY OBJECTIVE:

I. Evaluate whether the protocol specified primary biomarkers (both blood and imaging-based) measured at baseline, are associated with the future development of worrisome features and/or high-risk stigmata.

SECONDARY OBJECTIVES:

I. Evaluate whether the imaging-based secondary biomarker implemented using baseline computed tomography (CT) scans and/or the blood-based secondary biomarker panel, is associated with the future development of worrisome features and/or high-risk stigmata.

II. Estimate area under curve (AUC), sensitivity, specificity, negative, and positive predictive value of each biomarker.

III. Evaluate the predictive ability of the longitudinal trajectory of each biomarker for prediction of worrisome features and/or high-risk stigmata.

IV. Develop and evaluate risk scores that combine blood-based and imaging-based markers.

V. Compare patient reported outcomes (PROs) between study arms (A and B): quality of life (QOL), financial distress, and situational anxiety.

VI. Compare 5-year total cost between arms (A and B).

PRIMARY OBJECTIVE (PRIOR TO ADDENDUM #5 08/13/2024):

I. To compare the rates of unfavorable clinical outcomes in the two arms.

SECONDARY OBJECTIVES (PRIOR TO ADDENDUM #5 08/13/2024):

I. To compare rates of major surgical morbidity and/or mortality between arms. II. To compare pancreatic cancer incidence and all-cause mortality across arms. III. Compare institutional (direct) costs. IV. Compare healthcare utilization of imaging, invasive testing, surgical, and other procedures across the two surveillance arms.

V. Compare patient (out-of-pocket and other indirect) costs. VI. Describe diagnostic test and treatment pathways by arm. VII. Compare patient reports of QOL, situational anxiety. VIII. Compare patient report of financial distress. IX. Compare rates of non-adherence by arm assignment. X. To evaluate and compare the predictive performance of known and future biomarkers for dysplasia or cancer.

EXPLORATORY OBJECTIVE (PRIOR TO ADDENDUM #5 08/13/2024):

I. To evaluate and compare the predictive accuracy of known and future radiomic markers for dysplasia and pancreatic cancer.

OUTLINE: This is an observational study.

Patients undergo magnetic resonance imaging (MRI) or CT scans as well as blood sample collection throughout the trial. Patients undergo endoscopic ultrasound (EUS), fine needle aspiration (FNA), biopsy and surgery as clinically indicated.

Patients are followed up every 6 months or yearly for 5 years from the date of registration.

OUTLINE (PRIOR TO ADDENDUM #5 08/13/2024): This is an observational study. Patients are randomized to 1 of 2 arms.

ARM A (LOW INTENSITY SURVEILLANCE) (CLOSED TO ACCRUAL 08/13/2024): Patients undergo MRI, CT, or EUS at the beginning of the trial and MRI or CT again in 1 year. Following the first year, patients with no abnormalities repeat MRI or CT every 2 years. Patients with positive imaging features on MRI and CT at 1 or 2 years and with negative EUS, repeat MRI or CT in 1 year. Patients with negative imaging repeat MRI or CT in 2 years.

ARM B (HIGH INTENSITY SURVEILLANCE) (CLOSED TO ACCRUAL 08/13/2024): Patients undergo MRI, CT, or EUS at the beginning of the trial. Patients with >= 1 and < 2 cm cyst undergo MRI or CT every 6 months for 1 year, then every 12 months for 2 years, and then every 24 months thereafter. Patients with >= 2 and < 3 cm cyst undergo EUS within 6 months, and if EUS is negative, patients repeat MRI or CT in 1 year. If second EUS is negative, patients undergo alternate MRI or CT and EUS every 12 months. Patients with cyst >= 3 cm undergo alternate MRI or CT with EUS every 3-6 months.

All patients may also optionally undergo blood sample collection, biopsy and/or EUS-FNA on study.

After completion of imaging procedures, patients are followed up for 5 years from the date of registration.

Inclusion criteria

• Patient must be ≥ 50 years and ≤ 75 years of age
• Patient must not have acute pancreatitis or a history of chronic pancreatitis
• Patient must have received a CT, MRI, or EUS within 6 months prior to enrollment that revealed one or more ≥ 1 cm pancreatic cyst(s).
• Patients of childbearing potential must not be known to be pregnant
• Patient must not have a prior diagnosis of pancreatic malignancy of any type
• Patient must not have a history of pancreatic resection
• Patients with only pancreatic lesions without malignant risk (pancreatic pseudocyst or classic serous cystic lesion) are not eligible
• Patient must not have a family history of pancreatic adenocarcinoma in one or more first-degree relatives (biological parents, full siblings or children)
• Patient must not have pancreatic cyst morphology that would prompt immediate surgical consideration (enhancing mural nodule, solid component in cyst, pancreatic duct ≥ 10mm, cyst causing obstructive jaundice)
• Patient must not have a comorbid illness that precludes EUS or pancreatic cyst resection
• Patient must not be in any form of pancreatic cyst surveillance for > 1 year, defined as organized, periodic up-to-date imaging directed towards the pancreatic cyst of interest
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must be ≥ 50 years and ≤ 75 years of age
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have acute pancreatitis or a history of chronic pancreatitis.
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must have received a CT, MRI, or EUS within 6 months prior to randomization that revealed one or more ≥ 1 cm pancreatic cyst (s).
• PRIOR TO ADDENDUM #5 08/13/2024: Patients of childbearing potential must not be known to be pregnant.
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have a prior diagnosis of pancreatic malignancy of any type.
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have a history of pancreatic resection.
• PRIOR TO ADDENDUM #5 08/13/2024: Patients with only pancreatic lesions without malignant risk (pancreatic pseudocyst or classic serous cystic lesion) are not eligible.
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have a family history of pancreatic adenocarcinoma in one or more first-degree relatives (biological parents, full siblings or children).
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have pancreatic cyst morphology that would prompt immediate surgical consideration (enhancing mural nodule, solid component in cyst, pancreatic duct ≥10mm, cyst causing obstructive jaundice).
• PRIOR TO ADDENDUM #5 08/13/2024: Patient must not have a comorbid illness that precludes EUS or pancreatic cyst resection.