DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer

NCT ID: NCT02079363

Last Updated: 2014-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

330 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-08-31

Study Completion Date

2018-01-31

Brief Summary

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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

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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.

Conditions

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Pancreatic Diseases Pancreatic Neoplasms Pancreatitis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients with pancreatic adenocarcinoma

Exclusion criteria:

No prior cancer. No anticoagulant treatment.

No interventions, this is an observational study

Intervention Type OTHER

Patients with chronic pancreatitis

Exclusion criteria:

No prior cancer. No anticoagulant treatment.

No interventions, this is an observational study

Intervention Type OTHER

Patients with acute pancreatitis

Exclusion criteria:

No prior cancer.

No interventions, this is an observational study

Intervention Type OTHER

Patients screened for but not having upper GI cancer

Exclusion criteria:

No prior cancer.

No interventions, this is an observational study

Intervention Type OTHER

Interventions

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No interventions, this is an observational study

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aalborg University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery

MD, DMSc, Consultant surgeant, Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stine Dam Henriksen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark

Ole Thorlacius-Ussing, MD,DMSc,Prof

Role: STUDY_CHAIR

Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark

Locations

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Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital

Aalborg, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Stine Dam Henriksen, MD

Role: CONTACT

+45 97661210

June Lundtoft

Role: CONTACT

+45 97661131

Facility Contacts

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Stine Dam Henriksen, MD

Role: primary

+45 97661210

References

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Park JW, Baek IH, Kim YT. Preliminary study analyzing the methylated genes in the plasma of patients with pancreatic cancer. Scand J Surg. 2012;101(1):38-44. doi: 10.1177/145749691210100108.

Reference Type BACKGROUND
PMID: 22414467 (View on PubMed)

Melson J, Li Y, Cassinotti E, Melnikov A, Boni L, Ai J, Greenspan M, Mobarhan S, Levenson V, Deng Y. Commonality and differences of methylation signatures in the plasma of patients with pancreatic cancer and colorectal cancer. Int J Cancer. 2014 Jun 1;134(11):2656-62. doi: 10.1002/ijc.28593. Epub 2013 Nov 29.

Reference Type BACKGROUND
PMID: 24288256 (View on PubMed)

Park JK, Ryu JK, Yoon WJ, Lee SH, Lee GY, Jeong KS, Kim YT, Yoon YB. The role of quantitative NPTX2 hypermethylation as a novel serum diagnostic marker in pancreatic cancer. Pancreas. 2012 Jan;41(1):95-101. doi: 10.1097/MPA.0b013e318221c903.

Reference Type BACKGROUND
PMID: 21778928 (View on PubMed)

Liggett T, Melnikov A, Yi QL, Replogle C, Brand R, Kaul K, Talamonti M, Abrams RA, Levenson V. Differential methylation of cell-free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis. Cancer. 2010 Apr 1;116(7):1674-80. doi: 10.1002/cncr.24893.

Reference Type BACKGROUND
PMID: 20143430 (View on PubMed)

Jiao L, Zhu J, Hassan MM, Evans DB, Abbruzzese JL, Li D. K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking. Pancreas. 2007 Jan;34(1):55-62. doi: 10.1097/01.mpa.0000246665.68869.d4.

Reference Type BACKGROUND
PMID: 17198183 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24088737 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27891190 (View on PubMed)

Other Identifiers

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Hypmet

Identifier Type: -

Identifier Source: org_study_id

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