Pancreatic DiseasesNCT02079363
DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer
An observational study of Pancreatic Diseases and Pancreatic Neoplasms, run by Aalborg University Hospital at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis
- How many people
- 330 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2013to Jan 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Prior cancer history.
- Anticoagulant therapy.
- Immunological tissue disease.
Trial locations and contacts
1 site in 1 country.
June Lundtoft contact
Denmark1 site, 1 recruiting
- Recruiting
Research unit, Surgical Department of Gastroenterology, Aalborg University Hospital
Aalborg, 9000
Stine Dam Henriksen, MD, +45 97661210, stdh@rn.dk
About this study
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."
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
Read the 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.
- Conditions
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis
- Being tested
- No interventions, this is an observational study
- Keywords
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis, DNA promoter hypermethylation, DNA methylation, Cell-free DNA, Plasma
- Medical subject headings
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventions, this is an observational studyOther
| Study group | Role | What they receive |
|---|---|---|
| Patients with pancreatic adenocarcinoma | Exclusion criteria:
No prior cancer. No anticoagulant treatment. Receives: Other: No interventions, this is an observational study | |
| Patients with chronic pancreatitis | Exclusion criteria:
No prior cancer. No anticoagulant treatment. Receives: Other: No interventions, this is an observational study | |
| Patients with acute pancreatitis | Exclusion criteria:
No prior cancer. Receives: Other: No interventions, this is an observational study | |
| Patients screened for but not having upper GI cancer | Exclusion criteria:
No prior cancer. Receives: Other: No interventions, this is an observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of methylated genes for each participant.
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.
Measured: Time of diagnosis
Secondary outcomes (1)
Number of methylated genes for each participant related to prognosis
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.
Measured: 2 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study startAug 2013
- Primary completionAug 2017 (estimated)
- Study completionJan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Pancreatic DiseasesStudies of the same condition, open and under way.
- More trials run by Aalborg University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, Aalborg University Hospital
- Investigators
- Stine Dam Henriksen, MD, Principal investigator, Department of Gastrointestinal Surgery, Aalborg University Hospital, DenmarkOle Thorlacius-Ussing, MD,DMSc,Prof, Study chair, Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02079363
- Sponsor's protocol ID
- Hypmet
- Status last verified
- Jul 2014
- First submitted
- 4 Mar 2014
- Last updated
- 30 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22414467Melson 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.
PubMed 24288256Park 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.
PubMed 21778928Liggett 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.
PubMed 20143430Jiao 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.
PubMed 17198183Yi 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.
PubMed 24088737Henriksen 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.
PubMed 27891190
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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."
- ClinicalTrials.gov ID
- NCT02079363
- Acronym / sponsor ID
- Hypmet
- Conditions
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis
- Keywords
- Pancreatic Diseases, Pancreatic Neoplasms, Pancreatitis, DNA promoter hypermethylation, DNA methylation, Cell-free DNA, Plasma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Jan 2018 (estimated)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Patients with pancreatic adenocarcinoma | – | Other: No interventions, this is an observational studyExclusion criteria: No prior cancer. No anticoagulant treatment. |
| Patients with chronic pancreatitis | – | Other: No interventions, this is an observational studyExclusion criteria: No prior cancer. No anticoagulant treatment. |
| Patients with acute pancreatitis | – | Other: No interventions, this is an observational studyExclusion criteria: No prior cancer. |
| Patients screened for but not having upper GI cancer | – | Other: No interventions, this is an observational studyExclusion criteria: No prior cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (3 listed)
- Prior cancer history.
- Anticoagulant therapy.
- Immunological tissue disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventions, this is an observational study | Other | Patients screened for but not having upper GI cancer, Patients with acute pancreatitis, Patients with chronic pancreatitis, Patients with pancreatic adenocarcinoma |
Primary outcome
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.
1 secondary outcome
Number of methylated genes for each participant related to prognosis
Time frame: 2 years follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2014.
- Background: PubMed 22414467Park 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.
- Background: PubMed 24288256Melson 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.
- Background: PubMed 21778928Park 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.
- Background: PubMed 20143430Liggett 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.
- Background: PubMed 17198183Jiao 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.
- Background: PubMed 24088737Yi 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.
- Derived from this study: PubMed 27891190Henriksen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
June Lundtoft contact
Stine Dam Henriksen, MD principal investigator
Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
Ole Thorlacius-Ussing, MD,DMSc,Prof study chair
Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pancreatic Diseases and Pancreatic Neoplasms, run by Aalborg University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stine Dam Henriksen, MD (+45 97661210, stdh@rn.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of methylated genes for each participant. (time frame: Time of diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02079363, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2014.