Blood Markers of Early Pancreas Cancer

A Longitudinal Cohort Study to Identify Clinical and Blood Markers of Early Pancreas Cancer

Identifying biomarkers of early pancreatic ductal adenocarcinoma (PDAC) could facilitate screening for individuals at higher than average risk and expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.

The investigators propose a longitudinal study of subjects at higher than average risk of PDAC in order to generate clinical data and bank serial blood specimens.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; PreDiabetes; Genetic Predisposition to Disease; Chronic Pancreatitis; Inherited Disease; Pancreas Cyst
• Intervention / Treatment: Diagnostic test: Mixed Meal Tolerance Test; Diagnostic test: Hemoglobin A1c; Diagnostic test: Other exploratory blood biomarkers

Detailed Description

Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have only an 10% chance of surviving 5 years after diagnosis. Most PDAC is advanced and not amenable to curative therapies at the time of diagnosis, owing to lack of symptoms in early disease, nonspecific symptoms when they do develop resulting in a delay in diagnosis. Identifying biomarkers of early PDAC could facilitate screening for individuals at higher than average risk and expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.

The investigators propose a longitudinal study of subjects at higher than average risk of PDAC in order to generate clinical data and bank serial blood specimens. Subjects will include individuals with family history of pancreas cancer, individuals with cystic pancreas lesions or chronic pancreatitis, and individuals with new-onset diabetes. Identifying specific biomarkers - blood markers and/or a clinical "prodrome" - in participants who go on to develop PDAC could improve the diagnostic approach outcomes for patients diagnosed with PDAC.

• Study Type: Observational
• Enrollment (Estimated): 1250

Contacts and Locations

• Study Contact: Name: Suzanne M Wessling, RN, BSN; Phone Number: 402-559-1577; Email: suzanne.wessling@unmc.edu
• Study Contact Backup: Name: Kelsey A Klute, MD; Phone Number: 402-559-8500; Email: kelsey.klute@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • Unversity of Nebraska Medical Center
      • Contact: Suzanne M Wessling, RN, BSN; Phone Number: 402-559-1577; Email: suzanne.wessling@unmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

In order to obtain a resource of clinical data and longitudinally obtained, annotated blood specimens and to develop an enriched population to prospectively evaluate a sensitive and specific biomarker, subjects from the following 3 groups at higher than average risk of PDAC will be recruited and enrolled.

New onset diabetes, high risk pre-diabetes Pancreatic cystic neoplasms and pancreatitis Familial risk

Description

Inclusion Criteria:

General inclusion criteria:

1. Age ≥19
2. Able to provide written, informed consent
3. Able to to attend an in-person study visit in Omaha, NE twice a year to collect blood samples

Exclusion Criteria:

General exclusion criteria:

1. Personal history of PDAC
2. Currently receiving treatment for a cancer diagnosis (excluding long-term hormonal therapy)
3. Pre-diabetes on metformin for ≥ 3 years

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
New Onset Diabetes/High-Risk Prediabetes; Must meet one of the following criteria: New onset type 2 diabetes diagnosed within the past 3 years, defined as Hemoglobin A1c ≥ 6.5%*, fasting blood glucose >126mg/dL confirmed on a subsequent day or as diagnosed by a physician; High-risk pre-diabetes: Hemoglobin A1c >6.3% or A1c >6.0% with fasting blood glucose >110 or 2 hour oral glucose tolerance test between 140-200mg/dL; subjects who have been on metformin <3 years are eligible	Diagnostic test: Mixed Meal Tolerance Test; The goal of the test is to determine hormone secretion from the pancreas and small intestine in response to the mixed meal.; Other Names: MMTT; Diagnostic test: Hemoglobin A1c; This test provides the average level of blood glucose over the last 3 months.; Other Names: Glycated Hemoglobin Test; Glycosylated Hemoglobin; Diagnostic test: Other exploratory blood biomarkers; Other exploratory blood biomarkers including cell free DNA and other markers in development
Pancreatic Cystic Neoplasm/Pancreatitis; Must meet one of the following criteria: Pancreatic cystic neoplasm for which resection, endoscopic ultrasound or serial imaging has been recommended; Chronic pancreatitis as defined by cross-sectional imaging, endoscopic ultrasound, functional testing abnormalities OR as diagnosed by a gastroenterologist	Diagnostic test: Hemoglobin A1c; This test provides the average level of blood glucose over the last 3 months.; Other Names: Glycated Hemoglobin Test; Glycosylated Hemoglobin; Diagnostic test: Other exploratory blood biomarkers; Other exploratory blood biomarkers including cell free DNA and other markers in development
Inherited Risk; Must meet one of the following criteria: Two or more blood relatives with PDAC (includes 1st-3rd degree relatives as defined in Table 2); One 1st degree relative with PDAC diagnosed before age 60; Germline mutation associated with a higher than average risk of PDAC including but not limited to the following: Hereditary breast and ovarian cancer syndromes BRCA1, BRCA2, PALB2 Hereditary nonpolyposis colon cancer (Lynch) syndrome MLH1, MSH2, MSH6, PMS2 Familial adenomatous polyposis (APC) Familial atypical multiple melanoma and mole syndrome CKDN2a, p16 Peutz-Jeghers syndrome STK11 Ataxia-telangiectasia ATM Juvenile polyposis syndromes SMAD4, BMPR1A Li Fraumeni TP53 Cystic fibrosis and unaffected carriers CFTR; Personal or family history which meets clinical criteria for a hereditary cancer syndrome and includes a relative with PDAC	Diagnostic test: Hemoglobin A1c; This test provides the average level of blood glucose over the last 3 months.; Other Names: Glycated Hemoglobin Test; Glycosylated Hemoglobin; Diagnostic test: Other exploratory blood biomarkers; Other exploratory blood biomarkers including cell free DNA and other markers in development

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pancreas cancer cases diagnosed.	Number of pancreas cancer cases diagnosed.	10 years
Biomarkers which may predict early pancreas cancer.	Biomarkers which may predict early pancreas cancer.	10 years
Result of MMTT which may indicate type 3c diabetes, which may be a risk factor for pancreas cancer.	Result of MMTT which may indicate type 3c diabetes, which may be a risk factor	10 years

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Cancer Institute (NCI); VA Nebraska Western Iowa Health Care System; Virginia Mason Hospital/Medical Center
• Investigators: Principal Investigator: Kelsey A Klute, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 13, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Disease Attributes; Cysts; Digestive System Neoplasms; Diabetes Mellitus; Endocrine Gland Neoplasms; Pancreatic Diseases; Disease Susceptibility; Chronic Disease; Diabetes Mellitus, Type 2; Pancreatic Neoplasms; Pancreatitis; Pancreatitis, Chronic; Pancreatic Cyst; Genetic Predisposition to Disease; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Chrysarobin
• Other Study ID Numbers: 0335-18-FB; U01CA210240-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Pancreatic Cancer Detection Consortium (PCDC) includes collaborators at several institutions, including UNMC, working to identify biomarkers and develop novel imaging techniques to identify pre-malignant and subclinical PDAC. One of the primary objectives of the consortium is to establish a repository of serial biospecimens collected from subjects prior to their diagnosis of PDAC. These specimens will be readily available when biomarkers in development are ready for validation. Due to the low incidence of pancreas cancer, even in groups at substantially increased risk, obtaining enough specimens to use for biomarker identification from those subjects who go on to develop PDAC requires collaborative effort between multiple institutions. This proposal is the contribution from UNMC to the consortium's biorepository effort.
• IPD Sharing Time Frame: Data will be shared with the consortium on a rolling basis throughout the enrollment period.
• IPD Sharing Access Criteria: Priority will be given to researchers affiliated with the PCDC. Primary investigators will review outside requests, which may be accepted on a case by case basis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No