The primary objective is to study if PC surveillance in individuals with a CDKN2A or other high risk mutations leads to an increase of 5-year survival rate, as compared to PC in the general population. Secondary objectives are: (1) to study long-…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is the 5-year survival rate of patients with a CDKN2A
mutation undergoing surveillance who develop PC.
Secondary outcome
1) The 10-year survival rate of individuals with a high risk mutationof
patients with a CDKN2A mutation undergoing surveillance who develop PC.
2) Identification of risk factors that predict neoplastic progression and
development of PC.
3) The accuracy of MRI/MRCP and EUS for detecting neoplastic lesions, as
compared to histology as a reference.
4.1) The accuracy and feasibility of ct-DNA to detect PDAC.
4.2 The correlation between ct-DNA levels and PC stage.
4.3) The correlation between ct-DNA with CEA and CA 19-9 tumormarkers.
5) To explore the molecular profile of CDKN2A PDAC as compared to sporadic PDAC
(PDAC occurring in the general population).
6) Cost-effectiveness of pancreatic surveillance.
7) Exploration of psychological aspects of screening, including knowledge and
perceptions of benefits and risks of genetic testing and surveillance.
Background summary
Pancreatic cancer (PC) is a highly lethal malignancy. Early detection is
challenging due to the lack of recognizable symptoms in its early stages.
Although screening and detection of early PC and its precursor lesions may
improve outcomes, general population-based screening for average-risk
individuals is not recommended, because the average lifetime risk for
developing PC is too low. However, in individuals with a strong family history
and/or genetic susceptibility, pancreatic surveillance has the potential to
increase overall survival. Therefore, The International Cancer of the Pancreas
Screening (CAPS) Consortium guideline recommends pancreatic surveillance to
detect early PC and high-grade precursor lesions in high risk mutation
carriers, such as CDKN2A. Pancreatic surveillance should be organized in a
study setting which enables us to continuously evaluate and improve our
surveillance programs.
Study objective
The primary objective is to study if PC surveillance in individuals with a
CDKN2A or other high risk mutations leads to an increase of 5-year survival
rate, as compared to PC in the general population. Secondary objectives are:
(1) to study long-term survival; (2) to identify additional risk factors that
predict neoplastic progression in order to improve risk stratification; (3) to
evaluate the accuracy of MRI/MRCP and EUS for detecting neoplastic lesions; (4)
to investigate the role of ct-DNA as a diagnostic and prognostic marker; (5) to
investigate the molecular characteristics of CDKN2A PDAC; (6) to study the
cost-effectiveness of pancreatic surveillance; and (7) to explore the
psychological aspects of genetic testing and surveillance.
Study design
This study is a registry of CDKN2A and other high risk mutation carriers
enrolled in the Leiden University Medical Center PC surveillance program.
Study burden and risks
The majority of the data that will be collected in this study is part of
routine care. As a study procedure, we will collect two extra blood samples
during annual blood sampling, which is part of routine care. In addition, with
subset of participants (24-30 individuals) we will conduct a focus-group study
(in-depth interview), which will last a maximum of 2 hours. We feel that the
risks and burden in this study are neglectable. We expect that the study
outcomes may be directly beneficial for (future) individuals participating in
our surveillance program, and individuals participating in surveillance
programs in other expert centers.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must be
participating in the LUMC PC surveillance program, which requires:
- aged between 40 and 75, and
i) a proven CDKN2A or LKB1/STK11 mutation, regardless of family history, or
ii) a BRCA1/2, PALB2, ATM, MLH1/MSH2/MSH6 mutation with at least one first
degree relative with PC.
Exclusion criteria
- Comorbidity leading to an impaired physical performance (World health
organization (WHO) performance status 3-4) or mental retardation.
- Life expectancy <5 years
- Very limited understanding of the Dutch or English language to be able to
make an informed choice.
- No informed consent.
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL75802.058.21 |
| OMON | NL-OMON27120 |