Blood Markers of Early Pancreas Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 2, PreDiabetes, Pancreas Cyst, Chronic Pancreatitis, Genetic Predisposition to Disease, Inherited Disease

Intervention / Treatment
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* Diagnostic Test: Mixed Meal Tolerance Test
* Diagnostic Test: Hemoglobin A1c
* Diagnostic Test: Other exploratory blood biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General inclusion criteria: Age ≥19 Able to provide written, informed consent Able to to attend an in-person study visit in Omaha, NE twice a year to collect blood samples Exclusion Criteria: General exclusion criteria: Personal history of PDAC Currently receiving treatment for a cancer diagnosis (excluding long-term hormonal therapy) Pre-diabetes on metformin for ≥ 3 years

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| New Onset Diabetes/High-Risk Prediabetes<br>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<br>* The goal of the test is to determine hormone secretion from the pancreas and small intestine in response to the mixed meal.<br>* Other names: MMTT;Diagnostic Test: Hemoglobin A1c<br>* This test provides the average level of blood glucose over the last 3 months.<br>* Other names: Glycosylated Hemoglobin;Diagnostic Test: Other exploratory blood biomarkers<br>* Other exploratory blood biomarkers including cell free DNA and other markers in development<br>|
| Pancreatic Cystic Neoplasm/Pancreatitis<br>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<br>* This test provides the average level of blood glucose over the last 3 months.<br>* Other names: Glycosylated Hemoglobin;Diagnostic Test: Other exploratory blood biomarkers<br>* Other exploratory blood biomarkers including cell free DNA and other markers in development<br>|
| Inherited Risk<br>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<br>* This test provides the average level of blood glucose over the last 3 months.<br>* Other names: Glycosylated Hemoglobin;Diagnostic Test: Other exploratory blood biomarkers<br>* Other exploratory blood biomarkers including cell free DNA and other markers in development<br>|

What is the study measuring?
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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 |