Blood Markers of Early Pancreas Cancer

Recruiting

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

• Registration Number: NCT03568630
• Lead Sponsor: University of Nebraska

Brief Summary

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

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 participants at higher than average risk of PDAC in order to generate clinical data and bank serial blood specimens. Participants 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 Timeline

• Study First Submitted: 2018-06-13
• Study First Submitted QC: 2018-06-13
• Study First Posted: 2018-06-26
• Study Start: 2018-07-26
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-10
• Primary Completion: 2028-07
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1250

Inclusion Criteria

• Age ≥19

• Able to provide written, informed consent

• Able to attend an in-person study visit in Omaha, NE twice a year to collect blood samples

• Must also meet criteria for one specific cohort. Participants who meet criteria for more than one cohort are eligible. (The intent being that potential participants must meet the criteria for at least one cohort, but are eligible if criteria are met for more than one cohort)

  o New onset diabetes/high-risk pre-diabetes cohort: must meet one of the following criteria: New onset type 2 diabetes diagnosed within the past 3 years, defined as A1c ≥ 6.5%, fasting blood glucose >126mg/dL confirmed on a subsequent day or as diagnosed by a physician High-risk pre-diabetes: A1c >6.3% or A1c >6.0% with fasting blood glucose >110 or 2 hour oral glucose tolerance test between 140-200mg/dL, or taken metformin <3 years

  o Pancreatic cystic neoplasm/pancreatitis cohort: must have one of the following diagnoses: Pancreatic cystic neoplasm for which resection, endoscopic ultrasound (EUS) 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

  o Inherited risk cohort: must meet one of the following criteria: Two or more blood relatives with pancreatic ductal adenocarcinoma (PDAC), includes 1st-3rd degree relatives (First - parent, sibling or child; Second - grandparent, aunt/uncle, niece/nephew, or half-sibling; Third - first cousin, great grand parent or great grandchild) 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: 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-telangectasia (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 (as above)

Exclusion Criteria

• Personal history of pancreatic ductal adenocarcinoma (PDAC)
• Currently receiving treatment for a cancer diagnosis (excluding long-term hormonal therapy)
• Pre-diabetes on metformin for ≥ 3 years

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pancreatic Cystic Neoplasm/Pancreatitis	Other exploratory blood biomarkers	Must meet one of the following criteria: 1. Pancreatic cystic neoplasm for which resection, endoscopic ultrasound or serial imaging has been recommended 2. Chronic pancreatitis as defined by cross-sectional imaging, endoscopic ultrasound, functional testing abnormalities OR as diagnosed by a gastroenterologist
New Onset Diabetes/High-Risk Prediabetes	Hemoglobin A1c	Must meet one of the following criteria: 1. 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 2. 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
Pancreatic Cystic Neoplasm/Pancreatitis	Hemoglobin A1c	Must meet one of the following criteria: 1. Pancreatic cystic neoplasm for which resection, endoscopic ultrasound or serial imaging has been recommended 2. Chronic pancreatitis as defined by cross-sectional imaging, endoscopic ultrasound, functional testing abnormalities OR as diagnosed by a gastroenterologist
Inherited Risk	Hemoglobin A1c	Must meet one of the following criteria: 1. Two or more blood relatives with PDAC (includes 1st-3rd degree relatives as defined in Table 2) 2. One 1st degree relative with PDAC diagnosed before age 60 3. 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 4. Personal or family history which meets clinical criteria for a hereditary cancer syndrome and includes a relative with PDAC
Inherited Risk	Other exploratory blood biomarkers	Must meet one of the following criteria: 1. Two or more blood relatives with PDAC (includes 1st-3rd degree relatives as defined in Table 2) 2. One 1st degree relative with PDAC diagnosed before age 60 3. 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 4. Personal or family history which meets clinical criteria for a hereditary cancer syndrome and includes a relative with PDAC
New Onset Diabetes/High-Risk Prediabetes	Mixed Meal Tolerance Test	Must meet one of the following criteria: 1. 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 2. 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
New Onset Diabetes/High-Risk Prediabetes	Other exploratory blood biomarkers	Must meet one of the following criteria: 1. 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 2. 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

Primary Outcome Measures

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

Trial Locations

Locations (1)

Unversity of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States