DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer

July 29, 2014 updated by: Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, Aalborg University Hospital

Cell-free DNA Promoter Hypermethylation in Plasma From Patients With Pancreatic Adenocarcinoma, Compared to Patients With Pancreatitis and Pancreatitis and Patients Screened for, But Not Having Pancreatic Adenocarcinoma."

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

330

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Stine Dam Henriksen, MD
  • Phone Number: +45 97661210
  • Email: stdh@rn.dk

Study Contact Backup

  • Name: June Lundtoft
  • Phone Number: +45 97661131

Study Locations

  • Denmark
      • Aalborg, Denmark, 9000
        • Recruiting
        • Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital
        • Contact:
          • Stine Dam Henriksen, MD
          • Phone Number: +45 97661210
          • Email: stdh@rn.dk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with pancreatic adenocarcinoma, who were referred to Aalborg University Hospital between 2008 and 2012. Blodsamples are stored in a biobank.

Patients with chronic pancreatitis, who are hospitalized or have an outpatient visit at Aalborg University Hospital.

Patients with acute pancreatitis, who are hospitalized at Aalborg University Hospital.

Patients who are referred to Aalborg University Hospital for suspected upper GI cancer. Subsequent examinations invalidate the cancer diagnosis.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with pancreatic adenocarcinoma

Exclusion criteria:

No prior cancer. No anticoagulant treatment.
Other: No interventions, this is an observational study
Patients with chronic pancreatitis

Exclusion criteria:

No prior cancer. No anticoagulant treatment.
Other: No interventions, this is an observational study
Patients with acute pancreatitis

Exclusion criteria:

No prior cancer.
Other: No interventions, this is an observational study
Patients screened for but not having upper GI cancer

Exclusion criteria:

No prior cancer.
Other: No interventions, this is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of methylated genes for each participant.
Time Frame: 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.
Time of diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of methylated genes for each participant related to prognosis
Time Frame: 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.
2 years follow up

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of methylated genes in patients who are undergoing curative surgery.
Time Frame: 2 years follow up
We investigate the methylation status a of panel of 20 different genes in cell-free DNA in plasma from patients diagnosed with c. pancreas before curative surgery and after surgery and every 3 months for a 2 years periode. The purpose is to study the methylation status as a marker of recurrence.
2 years follow up
Number of methylated genes in patients with chronic pancreatitis.
Time Frame: 2 years follow up
We investigate the methylation status a of panel of 20 different genes in cell-free DNA in plasma form patients with chronic pancreatitis. The purpose is to se if the methylation profile changes during the course of chronic pancreatitis and to detect chronic pancreatitis patients with particular high risk of developing pancreatic cancer.
2 years follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aalborg University Hospital

Investigators

  • Principal Investigator: Stine Dam Henriksen, MD, Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
  • Study Chair: Ole Thorlacius-Ussing, MD,DMSc,Prof, Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Anticipated)

August 1, 2017

Study Completion (Anticipated)

January 1, 2018

Study Registration Dates

First Submitted

March 4, 2014

First Submitted That Met QC Criteria

March 4, 2014

First Posted (Estimate)

March 5, 2014

Study Record Updates

Last Update Posted (Estimate)

July 30, 2014

Last Update Submitted That Met QC Criteria

July 29, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hypmet

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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