Comparing Two Methods to Follow Patients With Pancreatic Cysts

Brief Summary

The purpose of this study is to compare two approaches for monitoring pancreatic cysts as well as to identify associated biomarkers. The study doctors want to compare more frequent monitoring versus less frequent monitoring as well as identify biomarkers which may improve risk detection of transformation to pancreatic cancer. The study doctors want to learn which monitoring method and which biomarkers lead to better outcomes for patients.

Brief Title

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

Detailed Description

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.

Categories

Endocrine System Cancers

Cancer

Gastrointestinal (GI) Cancers

Diabetes

Diabetes & Endocrine System

Digestive System

Liver

Completion Date

2031-12-31

Completion Date Type

Estimated

Conditions

PANCREATIC NEOPLASM

Eligibility Criteria

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.

Inclusion Criteria

Gender

All

Gender Based

false

Healthy Volunteers

Last Update Post Date

Wed, 05/27/2026 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Fri, 05/22/2026 - 12:00

Maximum Age

75 Years

Minimum Age

50 Years

NCT Id

NCT04239573

Org Class

Network

Org Full Name

Eastern Cooperative Oncology Group

Org Study Id

EA2185

Overall Status

Recruiting

Primary Completion Date

Tue, 12/31/2030 - 12:00

Primary Completion Date Type

Estimated

Official Title

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

Primary Outcomes

Outcome Description

Will assess the predictive performance of both primary markers separately. Time to first occurrence of worrisome features and/or high-risk stigmata will be measured from the time of baseline blood draw. Will use an overall significance level of 0.1. Will use a Bonferroni correction for multiplicity adjustment, the significance level applied to both primary biomarkers will be 0.05. Will evaluate using a two-sided log-rank test comparing time to occurrence of worrisome features and/or high-risk stigmata between the marker-positive and marker-negative subgroups. Will visually summarize time to occurrence of worrisome features and/or high-risk stigmata in both maker positive and marker negative using Kaplan-Meier curves. All biomarkers will come in with a predetermined threshold for determining marker positivity (as defined in their respective publications). The primary imaging marker is for MRI, the analysis of this biomarker will be restricted to participants with a pre-enrollment MRI.

Outcome Measure

Time-to-finding of a worrisome feature and/or high-risk stigmata on computed tomography (CT) or magnetic resonance imaging (MRI)

Outcome Time Frame

Up to 5 years

Outcome Description

Defined as a composite of: (1) any pancreatic cancer without surgery; (2) unresectable pancreatic cancer or cancer \> T1a, N0 at surgery, and (3) benign disease at surgery will be approached from the intent-to-treat perspective. Time to the first occurrence of the primary endpoint will be measured from randomization. Survival analysis methods will be used to estimate and compare distributions of time to an unfavorable event between the study arms. In particular Kaplan-Meier estimates will be developed for each arm and a log rank test will be used to compare the two arms.

Outcome Measure

Occurrence of an "unfavorable" outcome (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Time Frame

Up to 5 years

Secondary Ids

Secondary Id

NCI-2019-04790

Secondary Id

EA2185

Secondary Id

ECOG-ACRIN-EA2185

Secondary Id

EA2185

Secondary Outcomes

Outcome Description

Will evaluate with the analog analysis plan.

Outcome Time Frame

Up to 5 years

Outcome Measure

Finding of a worrisome feature and/or high-risk stigmata on CT or MRI

Outcome Description

Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety 4-item short form. The analysis group will be the patients recruited prior to the activation of addendum #5 and randomized to either high or low intensity surveillance. A hierarchical strategy will be used. Will compare situational anxiety between arms with a two-sample unequal-variance t-test.

Outcome Time Frame

Up to 5 years

Outcome Measure

Situational anxiety

Outcome Description

Will be measured using the PROMIS-10. The analysis group will be the patients recruited prior to the activation of addendum #5 and randomized to either high or low intensity surveillance. A hierarchical strategy will be used. Will compare quality of life between arms with a two-sample unequal-variance t-test.

Outcome Time Frame

Up to 5 years

Outcome Measure

Overall quality of life

Outcome Description

Will be measured using the Comprehensive Score for Financial Toxicity measure. The analysis group will be the patients recruited prior to the activation of addendum #5 and randomized to either high or low intensity surveillance. Will compare financial distress between arms with a two-sample unequal-variance t-test.

Outcome Time Frame

Up to 5 years

Outcome Measure

Financial distress

Outcome Description

Will evaluate the sum of Medicare reimbursement for all the healthcare utilization. Will compare total cost between arms. The analysis group will be the patients recruited prior to the activation of addendum #5 and randomized to either high or low intensity surveillance. The distribution of the cost will be examined. If it is approximately normal, then the cost between the arms will be compared using a t-test. Also, the variance in the cost will be compared to assess if it differs between the arms. If distribution is particularly skewed a transformation will be sought, and the comparison will be analyzed on that scale.

Outcome Time Frame

Up to 5 years

Outcome Measure

Cost

Outcome Description

Rates of major surgical morbidity and/or mortality will be estimated and compared across arms. All-cause mortality will be estimated and compared between the arms using log rank tests.

Outcome Time Frame

Up to 5 years

Outcome Measure

Surgical and all-cause mortality (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Rates of major surgical morbidity and/or mortality will be estimated and compared across arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Major surgical morbidity (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Pancreatic-cancer incidence and pancreatic cancer specific mortality will be estimated and compared between the arms using log rank tests.

Outcome Time Frame

Up to 5 years

Outcome Measure

Pancreatic cancer incidence (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will compare between two arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Institutional (direct) costs (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will compare between two arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Healthcare utilization of imaging, invasive testing, surgical, and other procedures (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will compare between two arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Patient (out-of-pocket and other indirect) costs (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will describe diagnostic test and treatment pathways by arm.

Outcome Time Frame

Up to 5 years

Outcome Measure

Diagnostic test and treatment pathways (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will be assessed by Patient Reported Outcomes Measurement Information System10. Will compare between arms. Longitudinal regression modelling will be completed to account for the repeated assessments over time.

Outcome Time Frame

Up to 5 years

Outcome Measure

Patient reports of quality of life (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will be assessed by Patient Reported Outcomes Measurement Information System-Anxiety short form. Will compare between arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Patient reports of situational anxiety (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will compare between arms.

Outcome Time Frame

Up to 5 years

Outcome Measure

Patient report of financial distress (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will compare rates of non-adherence by arm assignment.

Outcome Time Frame

Up to 5 years

Outcome Measure

Rates of non-adherence (PRIOR TO ADDENDUM #5 08/13/2024)

Outcome Description

Will evaluate and compare the predictive performance of known and future biomarkers for dysplasia or cancer.

Outcome Time Frame

Up to 5 years

Outcome Measure

Biomarker analysis (PRIOR TO ADDENDUM #5 08/13/2024)

Start Date

Tue, 06/16/2020 - 12:00

Start Date Type

Actual

Status Verified Date

Fri, 05/01/2026 - 12:00

First Post Date

Mon, 01/27/2020 - 12:00

First Post Date Type

Actual

First Submit Date

Thu, 01/16/2020 - 12:00

First Submit QC Date

Tue, 01/21/2020 - 12:00

Study Population

Patients with pancreatic cysts.

Std Ages

Adult

Older Adult

Maximum Age Number (converted to Years and rounded down)

Minimum Age Number (converted to Years and rounded down)

Investigators

Investigator Type

Principal Investigator

Investigator Name

John McAuliffe

Investigator Email

jomcauli@montefiore.org

Investigator Department

Surgery

Study Department

Surgery

Study Division

Please Specify

Categories Mesh Debug

Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS

Cancer --- NEOPLASMS BY SITE

Cancer --- NEOPLASMS

Endocrine System Cancers --- ENDOCRINE GLAND NEOPLASMS

Digestive System --- DIGESTIVE SYSTEM DISEASES