DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer

• Conditions: Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis
• Interventions: Other: No interventions, this is an observational study

• Registration Number: NCT02079363
• Lead Sponsor: Aalborg University Hospital

Brief Summary

The objectives of this project are to test whether alteration in DNA hypermethylation in plasma is:

* a diagnostic marker for pancreatic cancer

* a prognostic marker for pancreatic cancer

* a marker for recurrence of pancreatic cancer

* changing during the course of chronic pancreatitis, with the purpose of finding patients with high risk of developing pancreatic cancer

Detailed Description

Pancreatic cancer (PCa) is one of the most deadly cancers with a 5-year survival rate of less than 10 %. The majority of PCa are found to be none-resectable at the time of diagnosis. Only 10 - 20% of patients are offered surgical treatment, which is the only chance of cure. The mean survival times of none-resected patients are 3 to 6 months. Despite surgical treatment many patients experience recurrence. The high overall mortality is mainly caused by difficulties in early diagnosis due to unspecific/lack of symptoms in the early stages of the disease.

Patients with resectable tumors and no co-morbidity, have a 5-year survival rate up to 54 %. This indicates that early detection of the disease, which enables complete surgical resection of the tumor, is a way to improve survival. Chronic pancreatitis is one of the only known risk factors for PCa.

Currently there is no valid diagnostic marker for PCa. Diagnosis requires advanced methods and several of these are invasive and entail a risk of complications. A blood-based marker for pancreatic cancer would be a major achievement and of great benefit to the patients, and may even be used in screening.

During development of cancer changes in DNA arise, including DNA hypermethylation where a methyl residue is attached to the DNA. The methylation most frequently occurs in the regulatory region of the gene leading to inactivity. Some of the inactivated genes are necessary to ensure the control of cell growth. When these genes are inactivated, the cell will no longer be subject to normal control mechanisms and may eventually develop into a cancer cell.

Small amounts of DNA are released into the blood and can be detected in a blood sample. The DNA changes may be tumor specific and potentially useable as a marker for PCa. In 2012 our research unit in cooperation with Department of Molecular Diagnostic, Aalborg University Hospital published an optimized method for detection of hypermethylated DNA in plasma. The method has greatly improved sensitivity.

The purpose of our study is to test whether alterations in DNA hypermethylations in blood can be used as:

* A diagnostic marker for pancreatic cancer.

* A prognostic marker for pancreatic cancer.

* A marker for recurrence.

* Monitoring patients with chronic pancreatitis and detecting patients with particularly high risk of developing pancreatic cancer.

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2014-03-04
• Study First Submitted QC: 2014-03-04
• Study First Posted: 2014-03-05
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-29
• Last Update Posted: 2014-07-30
• Primary Completion: 2017-08
• Study Completion: 2018-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

• Patients with chronic pancreatitis who are hospitalized or have an outpatient visit at Aalborg University Hospital Or
• Patients hospitalized at Aalborg University Hospital, with acute pancreatitis verified by UL, CT or MR-scan and/or increased s-amylase

Exclusion Criteria

• Prior cancer history.
• Anticoagulant therapy.
• Immunological tissue disease.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with acute pancreatitis	No interventions, this is an observational study	Exclusion criteria: No prior cancer.
Patients with pancreatic adenocarcinoma	No interventions, this is an observational study	Exclusion criteria: No prior cancer. No anticoagulant treatment.
Patients with chronic pancreatitis	No interventions, this is an observational study	Exclusion criteria: No prior cancer. No anticoagulant treatment.
Patients screened for but not having upper GI cancer	No interventions, this is an observational study	Exclusion criteria: No prior cancer.

Primary Outcome Measures

Name	Time	Method
Number of methylated genes for each participant.	Time of diagnosis	We investigate the methylation status a of panel of 20 different genes in cell-free DNA in plasma. Plasma from patients with c. pancreas will be compared to plasma from patients in the control groups to se if DNA promoter hypermethylation can be used as a diagnostic marker for pancreas cancer.

Secondary Outcome Measures

Name	Time	Method
Number of methylated genes for each participant related to prognosis	2 years follow up	We investigate the methylation status a of panel of 20 different genes in cell-free DNA in plasma. Number of methylated genes will be investigated in relation to TNM- classification, tumor-size and time of survival.

Trial Locations

Locations (1)

Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital; 🇩🇰 Aalborg, Denmark