Clinical trial NCT02079363: DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer
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."
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pancreatic Diseases
Pancreatic Neoplasms
Pancreatitis
Keywords: Pancreatic Diseases
Pancreatic Neoplasms
Pancreatitis
DNA promoter hypermethylation
DNA methylation
Cell-free DNA
Plasma
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2014-03-05
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of methylated genes for each participant.
timeFrame: Time of diagnosis
Secondary outcomes:
measure: Number of methylated genes for each participant related to prognosis
timeFrame: 2 years follow up
Other outcomes:
measure: Number of methylated genes in patients who are undergoing curative surgery.
timeFrame: 2 years follow up
measure: Number of methylated genes in patients with chronic pancreatitis.
timeFrame: 2 years follow up
Locations:
city: Aalborg
country: Denmark
facility: Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital
Study officials:
affiliation: Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
name: Stine Dam Henriksen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
name: Ole Thorlacius-Ussing, MD,DMSc,Prof
role: STUDY_CHAIR
References:
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citation: Yi JM, Guzzetta AA, Bailey VJ, Downing SR, Van Neste L, Chiappinelli KB, Keeley BP, Stark A, Herrera A, Wolfgang C, Pappou EP, Iacobuzio-Donahue CA, Goggins MG, Herman JG, Wang TH, Baylin SB, Ahuja N. Novel methylation biomarker panel for the early detection of pancreatic cancer. Clin Cancer Res. 2013 Dec 1;19(23):6544-6555. doi: 10.1158/1078-0432.CCR-12-3224. Epub 2013 Oct 2.
citation: Henriksen SD, Madsen PH, Larsen AC, Johansen MB, Drewes AM, Pedersen IS, Krarup H, Thorlacius-Ussing O. Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma. Clin Epigenetics. 2016 Nov 16;8:117. doi: 10.1186/s13148-016-0286-2. eCollection 2016.