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Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk

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ClinicalTrials.gov Identifier: NCT02478892
Recruitment Status : Recruiting
First Posted : June 23, 2015
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:
The study is a prospective, observational study evaluating the utility of endoscopic ultrasound or MRI for the identification of preneoplastic and neoplastic pancreatic lesions in patients at high risk for pancreatic cancer, specifically those with BRCA1/2, ATM, or PALB2 mutations.

Condition or disease Intervention/treatment
Pancreatic Cancer Device: prophylactic endoscopic ultrasound or MRI of the abdomen

Detailed Description:

Endoscopic Ultrasound (EUS) has emerged as a critical component in the imaging, staging, and diagnosis of pancreatic cancer. Not only can EUS delineate a mass utilizing sonography through the wall of the stomach or duodenum, but it also can obtain diagnostic fine needle aspiration of suspicious lesions. Especially in patients with incomplete visualization of a mass on cross-sectional imaging, EUS can provide valuable anatomic information prior to surgical exploration. While several studies have demonstrated that EUS has high sensitivity and specificity in diagnosing pancreatic masses, head-to-head comparisons with established modalities like CT have been often methodologically flawed. In a meta-analysis, it was found that of 4 studies that assessed resectability, 2 showed no difference and 1 favored each modality. As such, estimates of accuracy for assessing preoperative resectability have also ranged in several studies from 63-93%. As such it has been recognized as an accepted modality for the evaluation of potential pancreatic malignany.

While screening in the general population is not feasible given the low incidence of PDAC, screening in high risk cohorts may allow for early detection of resectable, and potentially curable tumors. Clinical outcome of patients with smaller, non-metastasized tumors have a significantly improved 5-year survival. Generally the current recommendation is that patients who are first degree relatives of patients with PDAC from a familial PDAC kindred with at least 2 affected first-degree relatives, patients with Peutz-Jegher's syndrome, and patients with CDKN2A/BRCA1/BRCA2/ATM/PALB2/Lynch mutations with a first or second degree relative with pancreatic cancer would qualify for screening in the context of the CAPS5 trial. However, very recent evidence in a large Canadian study of pancreatic cancer patients demonstrated germline carrier status for BRCA1/2, and ATM in their cohort was associated with first degree relatives with breast and colorectal cancer but not pancreatic cancer, suggesting that we may have to re-evaluate criteria for pancreatic cancer screening in this population. Thus, the risk of pancreatic cancer development in this cohort of patients would not be addressed by the CAPS5 protocol, but would uniquely be addressed in our proposed study. In terms of modality, interval, and age to start/stop, there remains debate but generally annual EUS/MRI has been utilized. Therefore, amongst patients with increased risk of pancreatic cancer, like those with BRCA1/2, ATM, or PALB2 mutations, the successful identification of early neoplastic/preneoplastic lesions of the pancreas would allow for timely intervention and improved survival in this cohort and thus would be of high clinical relevance.

Thus we propose to utilize the unique cohort of increased risk patients followed at the University of Pennsylvania, to identify patients with BRCA1, BRCA2, ATM, or PALB2 mutations, regardless of family history of pancreatic cancer, and enroll them on an annual prospective pancreatic screening program. The hypothesis is that through early screening interventions, morbidity and mortality from this under-recognized malignancy in this high-risk patient population will be reduced.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk
Study Start Date : May 2015
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2027

Resource links provided by the National Library of Medicine



Intervention Details:
  • Device: prophylactic endoscopic ultrasound or MRI of the abdomen
    The patients will be followed up clinically with routine, prophylactic endoscopic ultrasound or MRI surveillance every 12 months for a duration of 10 years


Primary Outcome Measures :
  1. identifying pancreatic neoplastic lesions lesions in patients with BRCA1/2 mutations and other less common, but related mutations (ATM, PALB2) as well as mutations identified in the future. [ Time Frame: 10 years ]
    The primary objective of the study is the observational screening of patients with BRCA1/2, ATM, or, PALB2 mutations for pancreatic neoplastic lesions, to assess for both the feasibility of this approach in this high risk population as well as to better establish the incidence of these lesions in this cohort.


Biospecimen Retention:   Samples With DNA
For circulating colonic epithelial cell analysis, at least one ml whole blood will be required for analysis. A total of 40mL of blood will be collected for analysis.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients at high risk for pancreatic cancer, specifically those with BRCA1/2, ATM, or PALB2 mutations.
Criteria

Inclusion Criteria

  • Age >= 18
  • Documented germline pathogenic or likely pathogenic BRCA1, BRCA2, ATM, or PALB2 mutation
  • If no history of PDAC in a first or second degree relative, age >= 50
  • If there is a history of PDAC in a first or second degree relative, minimum age of eligibility is 10 years younger than the age of onset of the youngest relative with pancreatic cancer

Exclusion Criteria

• Pregnancy


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02478892


Contacts
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Contact: Bryson Katona, MD Bryson.Katona@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19004
Contact: Bryson Katona, MD    855-216-0098    Bryson.Katona@pennmedicine.upenn.edu   
Principal Investigator: Bryson Katona, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
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Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02478892    
Other Study ID Numbers: UPCC 26214
First Posted: June 23, 2015    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
high risk
specifically those with BRCA1/2 mutations
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases