DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Aalborg Universityhospital
Sponsor:
Information provided by (Responsible Party):
Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, Aalborg Universityhospital
ClinicalTrials.gov Identifier:
NCT02079363
First received: March 4, 2014
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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

Condition Intervention
Pancreatic Diseases
Pancreatic Neoplasms
Pancreatitis
Other: No interventions, this is an observational study

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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."

Resource links provided by NLM:


Further study details as provided by Aalborg Universityhospital:

Primary Outcome Measures:
  • Number of methylated genes for each participant. [ Time Frame: Time of diagnosis ] [ Designated as safety issue: No ]
    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:
  • Number of methylated genes for each participant related to prognosis [ Time Frame: 2 years follow up ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of methylated genes in patients who are undergoing curative surgery. [ Time Frame: 2 years follow up ] [ Designated as safety issue: No ]
    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.

  • Number of methylated genes in patients with chronic pancreatitis. [ Time Frame: 2 years follow up ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Cell free methylated DNA in EDTA plasma


Estimated Enrollment: 330
Study Start Date: August 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02079363

Contacts
Contact: Stine Dam Henriksen, MD +45 97661210 stdh@rn.dk
Contact: June Lundtoft +45 97661131

Locations
Denmark
Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital Recruiting
Aalborg, Denmark, 9000
Contact: Stine Dam Henriksen, MD    +45 97661210    stdh@rn.dk   
Sponsors and Collaborators
Aalborg Universityhospital
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
  More Information

Publications:

Responsible Party: Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, MD, DMSc, Consultant surgeant, Professor of Surgery, Aalborg Universityhospital
ClinicalTrials.gov Identifier: NCT02079363     History of Changes
Other Study ID Numbers: Hypmet
Study First Received: March 4, 2014
Last Updated: July 29, 2014
Health Authority: Denmark: Ethics Committee

Keywords provided by Aalborg Universityhospital:
Pancreatic Diseases
Pancreatic Neoplasms
Pancreatitis
DNA promoter hypermethylation
DNA methylation
Cell-free DNA
Plasma

Additional relevant MeSH terms:
Neoplasms
Pancreatitis
Pancreatic Neoplasms
Pancreatic Diseases
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014