Prospective Screening for Pancreatic Ductal Adenocarcinoma in High-Risk Individuals

Pancreatic Cancer Clinical Trial

Official title:

Prospective Screening for Pancreatic Ductal Adenocarcinoma in High-Risk Individuals

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06122896
• Other study ID #: 23-147
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 21, 2023
• Est. completion date: October 31, 2041

Study information

• Verified date: February 2024
• Source: Dana-Farber Cancer Institute
• Contact: Matthew Yurgelun, MD
• Phone: 617-582-8673
• Email: matthew_yurgelun[@]dfci.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to see if adding blood-based tests and symptom review to standard-of-care pancreatic cancer screening procedures can identify cancer early among individuals with increased risk.

Description:

In this research study, investigators will combine blood-based tests and review of symptoms with standard-of-care pancreatic cancer screening procedures to see if pancreatic cancer can be detected early among individuals with increased risk. Pancreatic cancer screening procedures include Endoscopic Ultrasound (EUS), Magnetic Resonance Imaging (MRI), or Magnetic Resonance Cholangiopancreatography (MRCP). The research study procedures include screening for eligibility, questionnaires, clinic visits, endoscopic ultrasound (EUS) or Magnetic Resonance (MRI)/Magnetic Resonance Cholangiopancreatography (MRCP), and collection of blood, stool, and saliva samples. Participation in this research study will be a minimum of 30 months and up to 20 years via review of medical records and the annual collection of blood and stool samples. It is expected that about 5,000 people will take part in this research study. This study is supported by the Hale Family Research Center at Dana-Farber Cancer Institute.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: October 31, 2041
• Est. primary completion date: October 31, 2040
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Participants must meet any of the following:

• Individuals with pathogenic/likely pathogenic germline variants in STK11, and age =30 years.
• Individuals with pathogenic/likely pathogenic germline variants in CDKN2A, and age =40 years (or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier).
• Individuals with pathogenic/likely pathogenic germline variants in one of the other pancreatic cancer susceptibility genes (ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, EPCAM, PALB2, TP53), and age =50 years (or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier) AND
• Exocrine pancreatic cancer in =1 first- or second-degree relative from the same side of (or presumed to be from the same side of) the family as the identified pathogenic/likely pathogenic germline variant.
• Individuals with pathogenic/likely pathogenic variants in PRSS1 AND a clinical phenotype consistent with hereditary pancreatitis, and age =40 years (or 20 years after onset of pancreatitis, whichever is earlier).
• Individuals with familial pancreatic cancer including:
• Family history of exocrine pancreatic cancer in =2 first-degree relatives from the same side of the family, even in the absence of a known pathogenic/likely pathogenic germline variant, OR
• Family history of exocrine pancreatic cancer in 1 affected first-degree relative and 1 second-degree relative, even in the absence of a known pathogenic/likely pathogenic germline variant, OR
• Family history of exocrine pancreatic cancer in =3 first- and/or second-degree relatives from the same side of the family, even in the absence of a known pathogenic/likely pathogenic germline variant.
• Individuals who are undergoing clinically recommended pancreatic cancer surveillance.

Exclusion Criteria:

• Individuals with active or prior pancreatic ductal adenocarcinoma diagnosis.
• Individuals with any active metastatic cancer.
• Individuals who are unable to give informed consent.
• Individuals who are under the age of 18 (infants, children, teenagers).
• Individuals unable to tolerate Magnetic Resonance Imaging/Magnetic Resonance Cholangiopancreatography and Endoscopic Ultrasound.
• Pregnant women are unlikely to be undergoing screening procedures and will not be considered eligible but can consent to the study at a later date.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasm
• Pancreatic Neoplasms
• PDAC
• PDAC - Pancreatic Ductal Adenocarcinoma

Intervention

Other:
• Screening Blood Tests
Carbohydrate antigen (CA) 19-9, Hemoglobin A1C (HbA1c), and Fasting blood glucose (FBG) per standard-of-care.

Diagnostic Test:
• Endoscopic Ultrasound
Annually and per National Comprehensive Cancer Network Guidelines (NCCN) guidelines.

Combination Product:
• Magnetic Resonance Imaging
Annually and per National Comprehensive Cancer Network Guidelines (NCCN) guidelines.
• Magnetic Resonance Cholangiopancreatography
Annually and per National Comprehensive Cancer Network Guidelines (NCCN) guidelines.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Incident Pancreatic Cancers or High-Grade Pancreatic Neoplasms	Subjects will be counted in this metric if they have pathological tissue confirmation of a pancreatic cancer or high-grade dysplasia during each observation period.	6-monthly for 3 years with 5-year follow-up
Primary	Number of Imaging-Positive Pancreatic Cancers or High-Grade Neoplasms	Subjects will be considered imaging-positive if they have a biopsy-confirmed pancreatic ductal adenocarcinoma or high-grade dysplasia that was initially detected on standard-of-care screening MRI or EUS during each observation period.	6-monthly for 3 years with 5-year follow-up
Primary	Number of Imaging-Negative, Assay-Positive Pancreatic Cancers or High-Grade Neoplasms	Subjects will be considered imaging-negative and assay-positive if: 1) the subject has a study visit that yields any newly positive CA19-9 (>35U/mL or >=20% increase) or diabetes (FBG >100mg/dL for first time or HgbA1c increased by 0.5) assay result or ENDPAC score >=3 with negative MRI and/or EUS at that visit or within six months prior to that visit; and 2) has a biopsy-confirmed pancreatic ductal adenocarcinoma or high-grade dysplasia within two years after that visit.	6-monthly for 3 years with 5-year follow-up
Secondary	Positive Predictive Value of Blood Assays	Positive predictive value of blood assays, defined as newly positive CA19-9 (>35U/mL or >=20% increase) or diabetes (FBG >100mg/dL for first time or HgbA1c increased by 0.5) assay result or ENDPAC score >=3, with a positive biopsy for PDAC or High-Grade Dysplasia within six months divided by the total number with a positive blood assay.	6-monthly for 3 years
Secondary	Negative Predictive Value of Blood Assays	Negative predictive value of blood assays, defined as CA19-9 (<=35U/mL or <20% increase) or diabetes (FBG <100mg/dL for first time or HgbA1c increased by less than 0.5) assay result or ENDPAC score <3, without a positive biopsy for PDAC or High-Grade Dysplasia within six months divided by the total number with a negative blood assay.	6-monthly for 3 years
Secondary	Proportion of Screen-Detected, Resected Pancreatic Lesions	Number of screen-detected pancreatic lesions that are resected compared to the total number of screen-detected pancreatic lesions.	6-monthly for 3 years
Secondary	Proportion of Non-Worrisome Pancreatic Lesions	Number of pancreatic lesions that are biopsied without cancer or high-grade dysplasia divided by number of pancreatic lesions that are biopsied.	6-monthly for 3 years
Secondary	Incremental Yield of Blood-Based Assays over Standard-of-Care Screening	Number of imaging-negative, assay-positive cases showing cancer or high-grade dysplasia divided by the total number of imaging-negative cases with cancer or high-grade dysplasia.	6-monthly for 3 years
Secondary	Number of False-Positive Assay Results	Number of positive assay results, defined as newly positive CA19-9 (>35U/mL or >=20% increase) or diabetes (FBG >100mg/dL for first time or HgbA1c increased by 0.5) assay result or ENDPAC score >=3, without a clinical diagnosis of pancreatic cancer within one year.	6-monthly for 3 years
Secondary	Number of Non-PDAC Cancer Diagnoses	Number of non-PDAC cancer detected through blood-based assays, EUS and/or MRI during the active screening period.	6-monthly for 3 years
Secondary	Clinical Predictors of Neoplastic Development	Frequencies of clinical predictors of neoplastic development as indicated by responses to the study surveys.	up to 8 years