The Influence of Secretin Stimulated Pancreatic Secretion on ctDNA Expression in Patients With Pancreatic Ductal Adenocarcinoma: The Role of Biomarkers in Determining the Prognosis of Pancreatic Ductal Adenocarcinoma

February 3, 2025 updated by: Charles University, Czech Republic

The Influence of Secretin Stimulated Pancreatic Secretion on Circulating Tumor DNA Expression in Patients With Pancreatic Ductal Adenocarcinoma: The Role of Biomarkers in Determining the Prognosis of Pancreatic Ductal Adenocarcinoma

The goal of this study is to assess the influence of pancreatic secretion stimulation by intravenously administered secretin on circulating tumor DNA in patients with pancreatic ductal adenocarcinoma. Additional aim of the study is to analyse a role of specific biomarkers in determining the prognosis of this disease. The main question o answer is:

Does intravenous secretin administration potentiate the release of circulating tumor DNA in patients with pancreatis ductal adenocarcinoma?

Additional question is:

Is there a biomarker specific and sensitive enough to help to predict the prognosis and the at the time status of the disease?

Participants scheduled for surgical treament due to pancreatic ductal adenocarcinoma will be included and stimulated with intravenously administered secretin, their peripheral blood samples will then be analyzed for ctDNA levels.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive oncological disease with a poor prognosis and low survival rate. Due to its biological nature, it is generally challenging to accomplish early diagnostics and therefore to achieve successful therapeutic results.

Recently, many trials and studies worldwide aim at better understanding of tumor biology and providing a novel tool for diagnostics, disease monitoring and developing a targeted therapy. One of the subjects of interest happen to be the so-called liquid biopsies.

Isolation of biomarkers such as miRNA, tumor suppressor genes or amino acids from these biopsies, their analysis, quantification and incorporation into clinical oncology represents a complex issue where further research is highly required. Subjects, materials, methods A crucial prerequisite for biomarker analysis is a sufficient amount of genetic information. In our study, the effect of intravenous secretin administration on ctDNA release in patients with PDAC will be analysed. More than 90% KRAS mutation rate in patients with PDAC has been scientifically proven, therefore patients with positive KRAS mutation in their peripheral blood plasma and scheduled for surgical therapy will be included in the study.

Peripheral blood plasma of 36 patients with PDAC diagnosis will then be collected in specific intervals during the first two hours of the operation. Plasmatic levels of ctDNA in the samples will be quantified. A standardized panel of biomarkers will be designed and tested in patients with PDAC prior to surgery and in specific intervals after surgery. The results will be analyzed in correlation to minimal residual disease, survival rate and other indicators to determine the prognosis of the disease. Statistic evaluation will be done in cooperation with specialists experienced in bioinformatics and biomedical statistics.

Introduction:

Pancreatic ductal adenocarcinoma (PDAC) ranks among the most serious and aggressive malignant diseases with an unfavorable prognosis and high mortality [1,2]. Five year survival for patients with PDAC is 10 %, and ten-year survival is 6 % [3]. According to the Institute of Health Information and Statistics of the Czech Republic, incidence of PDAC in Czechia is 21.9/100000 inhabitants, prevalence is 23,2/100000 inhabitants. In addition to insufficient response to systemic chemotherapy, this statistic also contributes significantly to the difficulty of early detection of the disease due to its often asymptomatic period, while treatment methods may be significantly limited at the time of diagnosis. The indication of surgical treatment as a potentially curative method clearly depends on the established extent of the disease [4]. Currently, the worldwide monitored marker is the level of Ca19-9 in the serum, also in relation to the determination of preoperative and postoperative prognosis [5]. However, due to the lack of sufficient sensitivity and specificity for PDAC, Ca19-9 cannot be classified as a specific marker with sufficient predictive value [6]. More than three hundred markers have been proposed in various biological materials (blood, urine, feces, saliva, bile, pancreatic juice, etc.) for screening, early diagnosis, response to treatment and prognosis, but none of the biomarkers currently has a wider application in daily clinical practice [6,7].

According to recent studies, several biomarkers [6] have been identified with a high potential for further investigation in correlation with the assessment of prognosis and future use in screening in the general population [6,7,8] Early diagnosis is a key part of treatment options and the prognosis improvement in PDAC, therefore a set of biomarkers with significant potential for practical clinical use was chosen for this project to be analyzed. One of those is KRAS protooncogene from the RAS family, which is frequently mutated in PDAC [9, 10, 11, 12]. The mutated KRAS gene is about to be detected from the ctDNA isolated from the patient's plasma before and after intravenous stimulation with secretin, a hormone responsible also for pancreatic secretion [13]. We suppose that the secretin stimulation is going to potentiate the release of ctDNA.

Analysis of mutant KRAS, mRNA, miRNA, siRNA, exoRNA, S100 proteins and amino acids could therefore become an efficient hallmark in PDAC monitoring during the diagnostic - therapeutic process.

Objectives:

The aim of this project is to prove the potentiating influence of intravenous secretin stimulation on ctDNA release in patients with PDAC and thereby mediate higher plasmatic levels of ctDNA potentially usable for further analysis. Besides that, the role of KRAS mutation in ctDNA, mRNA, miRNA, siRNA, exoRNA, S100 proteins and amino acids is about to be analyzed throughout the therapeutic process to monitor the correlation of the marker levels to the standardized indicators of life expectancy, quality of life etc. at a time.

Zero hypothesis:

The plasmatic level of ctDNA after intravenous secretin administration will not be significantly higher than before the administration. The plasmatic levels of mRNA, miRNA, exogenic RNA and S100 proteins will not be significantly lower after surgery than prior to surgery and they will not show any correlation with postoperative course of the disease.

Methodology and statistic evaluation:

In the first phase, both male and female patients in any age-range diagnosed with PDAC and indicated for surgical therapy will be selected. Considering multiple blood sample collections in a short period of time, physiological effects of secretin and logistic optimization of the process, we have decided to involve the patients indicated for surgery.

Patients with tumor duplicity will be excluded. Only the patients with signed consent of participation in the study will be included. These patients' blood plasma will be collected from a peripheral vein during an outpatient visit prior to surgery and tested for the positivity of mutated KRAS gene with heteroduplex analysis using denaturing capillary electrophoresis.

36 patients with KRAS positive plasma sample will then be routinely prepared for surgery. In the first two hours of the surgical procedure, 16 micrograms of intravenous secretin will be applied. During this period of time, the intravenous secretin administration to the patient is safe and will not interfere with the surgical phase of pancreatic resection. In the interval of 3 minutes and 3x 5 minutes from the secretin application, blood samples will be collected from the peripheral vein as well by the anesthesia personnel. All blood samples will be collected to the prepared sampling kits with no need for further technical processing, transported to the laboratory and subjected for the analysis and quantification of ctDNA ant other candidate markers. In the second phase of the project, the most promising marker panels will be established based on the current knowledge and preliminary results. Blood plasma of the patients diagnosed with PDAC, indicated for surgical therapy will then be tested for the marker levels preoperatively and postoperatively before dismissal, 3, 6 and 12 months after surgery during outpatient examination. The results will then be analyzed and evaluated statistically in correlation with minimal residual disease, survival rate, quality of life and other standardized indicators to monitor the prognosis of the disease. Statistic evaluation will be realized in cooperation with specialists with a broad experience in bioinformatics and biomedical statistics.

Outcomes and significance:

Our project will provide a systematic literature review regarding liquid biopsy and biomarker analysis and its incorporation to clinical oncology in patients diagnosed with PDAC. The effect of intravenous administration of secretin on ctDNA release to patients with PDAC as an innovative method will be analyzed, potentially procuring a significantly larger amount of genetic information for biomarker analysis in these patients. Moreover, the results and outcome will help to design a panel of biomarkers and to evaluate their clinical implication in disease monitoring and prognosis evaluation.

Study Type

Observational

Enrollment (Estimated)

39

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

Study Contact Backup

Study Locations

  • Czechia
      • Prague, Czechia, 16902
        • Department of Surgery, Military University Hospital in Prague
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Subjects will be recruited as citizens of either Czech or Slovak republic, in any age-range, examined at various departments such as Gastroenterology, Surgery, Radiology in various healthcare facilities, recommended for multidisciplinary tumor board as a part of the Pancreatic Surgery Center, Department of Surgery, Military University Hospital in Prague.

Description

Inclusion Criteria:

  • patients diagnosed with pancreatic ductal adenocarcinoma
  • patients indicated for surgery by multidisciplinary tumor board
  • patients without previously administered chemotherapy
  • patients with previously administered chemotherapy

Exclusion Criteria:

  • patients diagnosed with pancreatic ductal adenocarcinoma, at the time indicated for different than surgical therapy

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with pancreatic ductal adenocarcinoma scheduled for surgery
Both male and female patients of all age diagnosed with pancreatic ductal adenocarcinoma and indicated for surgical treatment by multidisciplinary tumor board. Patients with and without previously completed chemotherapy will be included.
Other: Intravenously administered secretin
16 micrograms of liquid secretin will be one-time intravenously administered to patients with PDAC during the first hour of surgery. Four peripheral blood samples will then be collected. Plasmatic levels of ctDNA will be measured. Plasmatic levels of biomarkers such as mRNA, miRNA, siRNA, exoRNA, S100 proteins and amino acids, isolated from the same blood samples, will be measured and analyzed in correlation to tumor volumometry, survival rate etc. in specific intervals during follow-ups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasmatic level of circulating tumor DNA
Time Frame: During the surgery: 3, 8, 13, 18 minutes after secretin administration; 3, 6 and 12 months after surgery
ng/ml
During the surgery: 3, 8, 13, 18 minutes after secretin administration; 3, 6 and 12 months after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasmatic levels of mRNA, miRNA, S100 proteins, siRNA, exoRNA.
Time Frame: During the surgery: 3, 8, 13, 18 minutes after secretin administration; 3, 6 and 12 months after surgery.
ng/ml
During the surgery: 3, 8, 13, 18 minutes after secretin administration; 3, 6 and 12 months after surgery.

Collaborators and Investigators

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

Sponsor

Charles University, Czech Republic

Collaborators

Military University Hospital in Prague, Czech Republic

Investigators

  • Study Director: Jan Bureš, prof., MD, CSc., FCMA, Military University Hospital in Prague
  • Principal Investigator: Kristýna Pončáková, MD, Military University Hospital in Prague

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

Helpful Links

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 (Estimated)

February 9, 2025

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 29, 2025

First Submitted That Met QC Criteria

February 3, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 3, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01012025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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