Clinical trial NCT02478892: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with Inherited Genetic Risk
Official title: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with Inherited Genetic Risk
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Cancer
Keywords: high risk
specifically those with BRCA1/2 mutations
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2015-06-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients at high risk for pancreatic cancer, specifically those with pathogenic germline variant in BRCA1, BRCA2, ATM, or PALB2 who will be undergoing pancreatic cancer screening as part of their routine clinical care.

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.

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 malignancy.

While pancreatic ductal adenocarincoma (PDAC) 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 directly related relatives, patients with Peutz-Jeghers syndrome, those with a CDKN2A pathogenic germline variant, and those with BRCA1/BRCA2/ATM/PALB2/Lynch pathogenic germline variants with a first or second degree relative with pancreatic cancer would qualify for pancreatic cancer screening. However, there is continued debate about whether family history should be used to determine who is eligible for pancreatic cancer screening. In this study we will be following individuals at the University of Pennsylvania who have a BRCA1, BRCA2, ATM, or PALB2 pathogenic germline variant and who are getting pancreatic cancer screening, regardless of whether or not they have a family history of PDAC. Ultimately, in high-risk individuals, such as BRCA1/2, ATM, and PALB2 carriers, the successful identification of early neoplastic/preneoplastic lesions of the pancreas would allow for timely intervention and likely improved survival in this cohort.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
References:
citation: Katona BW, Long JM, Ahmad NA, Attalla S, Bradbury AR, Carpenter EL, Clark DF, Constantino G, Das KK, Domchek SM, Dudzik C, Ebrahimzadeh J, Ginsberg GG, Heiman J, Kochman ML, Maxwell KN, McKenna DB, Powers J, Shah PD, Wangensteen KJ, Rustgi AK. EUS-based Pancreatic Cancer Surveillance in BRCA1/BRCA2/PALB2/ATM Carriers Without a Family History of Pancreatic Cancer. Cancer Prev Res (Phila). 2021 Nov;14(11):1033-1040. doi: 10.1158/1940-6207.CAPR-21-0161. Epub 2021 Aug 2.