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Pancreatic Cancer Screening in a Population at High Risk

Not Applicable
Recruiting
Conditions
Pancreatic Ductal Adenocarcinoma
Hereditary Diseases
Pancreatitis, Chronic
Interventions
Procedure: endoscopic ultrasonography
Procedure: magnetic resonance
Diagnostic Test: laboratory examination
Registration Number
NCT06330441
Lead Sponsor
Masaryk Memorial Cancer Institute
Brief Summary

Pancreatic cancer is one of the diseases with the worst prognosis, which is mainly due to the initial asymptomatic prognosis. Unfortunately, the incidence of this disease in the Czech Republic is still increasing. In a certain proportion of patients, it is possible to predict the disease, e.g. due to family burdens. Regular follow-up of such individuals is the subject of the SCREPAN study: "Pancreatic Cancer Screening in High-Risk Persons".

Detailed Description

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the worst prognosis. Mortality in this disease is almost equal to the incidence. In the Czech Republic, the incidence of this cancer has an upward trend, in 2017, 21.2 new cases per 100,000 people were reported, which represents a more than double increase compared to the data from the 1970s.

Pancreatic cancer is associated with an extremely poor prognosis for several reasons. It is usually diagnosed at an advanced stage, which is often due to the asymptomatic course of the disease or non-specific symptoms, the lack of sensitive and specific tumor markers, and difficult diagnosis by imaging methods in the early stages. Five-year survival, regardless of clinical stage, is between 7-9%.

Resectable disease is diagnosed in only 10% of patients, in which the 5-year survival rate is 37 %, locally advanced unresectable disease is detected in about 30 % of patients with a 5-year survival of 12 %, and metastatic disease is found in about 60 % of patients, with a 5-year survival rate of only around 3 %.

The poor prognosis of this disease is also due to the limited possibilities of screening and curative intervention for a short "lead time" in rapidly metastatic disease.

Pancreatic cancer screening is not suitable for the non-selected population. On the contrary, it is important for individuals with a high risk of developing this disease. In these subjects, early diagnosis during screening demonstrated a higher number of curative resections and longer survival.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
700
Inclusion Criteria
  • willing to participate in the study
  • age 18+
  • arms specific criteria:

A:

  • chronic pancreatic disease in the context of cystic fibrosis or chronic pancreatitis
  • age 50+

B1:

  • confirmed Peutz-Jegherson syndrome (mutSTK11) + age over 35 years or 10 years earlier than pancreatic ductal adenocarcinoma was diagnosed in the youngest family member
  • familial melanoma syndrome (mutCDKN2A) + age over 40 years or 10 years before pancreatic ductal adenocarcinoma was diagnosed in the youngest family member
  • confirmed hereditary pancreatitis (mutPRSS1) + age over 40 years or 20 years after the first attack

B2:

  • confirmed diagnosis of hereditary syndrome (Lynch syndrome /mutMLH1, mutMSH2, mutMSH6, mutPMS2, mutEPCAM/, HBOC /mutBRCA1, mutBRCA2, mutPALB2, mutATM/, familial adenomatous polyposis /mutAPC/, Li-Fraumeni syndrome /mutTP53/)
  • at least one relative with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis at the same time (Grade I or II relative)
  • age over 50 years, or 10 years before the pancreatic ductal adenocarcinoma was diagnosed in the youngest relative - which comes first

C:

  • positive family anamnesis of pancreatic ductal adenocarcinoma without hereditary syndrome context
  • age 50+ or 10 years earlier than the youngest relative with pancreatic ductal adenocarcinoma - screening is recommended for all first-degree relatives of affected family members
Exclusion Criteria
  • Inability to undergo radical curative surgery for a pancreatic tumor.
  • Inability to undergo scheduled imaging examinations.
  • Incurable malignant cancer.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
A - chronic pancreatitislaboratory examinationChronic pancreatitis, due to cystic fibrosis
B2 - genetic predisposition of hereditary syndromesmagnetic resonancePersons with a confirmed diagnosis of hereditary syndromes and at the same time with the condition of at least one relative of the first or second degree with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis; i.e. Lynch syndrome (mut: MLH1, MSH2, MSH6 a PMS2, EPCAM), HBOC (mut: BRCA1, BRCA2, PALB2, ATM), familial adenomatous polyposis (mut: APC), Li-Fraumeni syndrome (mut: TP53)
C - positive family anamnesisendoscopic ultrasonographyPersons with positive family anamnesis of pancreatic ductal adenocarcinoma without proven hereditary syndrome
A - chronic pancreatitisendoscopic ultrasonographyChronic pancreatitis, due to cystic fibrosis
B1 - genetic predisposition (STK11, CDKN2A, PRSS1)laboratory examinationPersons with a confirmed diagnosis of Peutz-Jeghers syndrome (STK11 mutation) or familial melanoma syndrome (CDKN2A mutation), hereditary pancreatitis (PRSS1 mutation)
A - chronic pancreatitismagnetic resonanceChronic pancreatitis, due to cystic fibrosis
B2 - genetic predisposition of hereditary syndromeslaboratory examinationPersons with a confirmed diagnosis of hereditary syndromes and at the same time with the condition of at least one relative of the first or second degree with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis; i.e. Lynch syndrome (mut: MLH1, MSH2, MSH6 a PMS2, EPCAM), HBOC (mut: BRCA1, BRCA2, PALB2, ATM), familial adenomatous polyposis (mut: APC), Li-Fraumeni syndrome (mut: TP53)
C - positive family anamnesislaboratory examinationPersons with positive family anamnesis of pancreatic ductal adenocarcinoma without proven hereditary syndrome
B1 - genetic predisposition (STK11, CDKN2A, PRSS1)endoscopic ultrasonographyPersons with a confirmed diagnosis of Peutz-Jeghers syndrome (STK11 mutation) or familial melanoma syndrome (CDKN2A mutation), hereditary pancreatitis (PRSS1 mutation)
C - positive family anamnesismagnetic resonancePersons with positive family anamnesis of pancreatic ductal adenocarcinoma without proven hereditary syndrome
B1 - genetic predisposition (STK11, CDKN2A, PRSS1)magnetic resonancePersons with a confirmed diagnosis of Peutz-Jeghers syndrome (STK11 mutation) or familial melanoma syndrome (CDKN2A mutation), hereditary pancreatitis (PRSS1 mutation)
B2 - genetic predisposition of hereditary syndromesendoscopic ultrasonographyPersons with a confirmed diagnosis of hereditary syndromes and at the same time with the condition of at least one relative of the first or second degree with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis; i.e. Lynch syndrome (mut: MLH1, MSH2, MSH6 a PMS2, EPCAM), HBOC (mut: BRCA1, BRCA2, PALB2, ATM), familial adenomatous polyposis (mut: APC), Li-Fraumeni syndrome (mut: TP53)
Primary Outcome Measures
NameTimeMethod
Number of participants with newly diagnosed pancreatic ductal adenocarcinomaFrom date of subject enrollment annualy in determined examinations according to the protocol schedule until the date of PDAC diagnosis or up to 60 months of subject participation in the study

Number of participants (in risk population) with newly diagnosed pancreatic cancer

Secondary Outcome Measures
NameTimeMethod
Screening methods cost-effectivenessthrough study completion, an average of 1 year

Comparison of magnetic resonance versus endoscopic ultrasonography cost effectiveness

KRAS mutation status evaluationFrom the date of subject enrollment annualy in determined examinations according to the protocol schedule until the date of PDAC diagnosis or up to 60 months of subject participation in the study

KRAS mutation status defined by number of positive droplets on drop digital PCR using material from liquid biopsy

Methods yield comparisonthrough study completion, an average of 1 year

Comparison of magnetic resonance versus endoscopic ultrasonography yield

Trial Locations

Locations (1)

Masaryk Memorial Cancer Institute

🇨🇿

Brno, Czechia

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