Clinical trial NCT06258824: MicroRNAs as Bile-based Biomarkers in Pancreaticobiliary Cancers
Official title: MicroRNAs as Bile-based Biomarkers in Pancreaticobiliary Cancers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Cancer
Cholangiocarcinoma
Ampullary Cancer
Biliary Stricture
Gallstone Disease
Keywords: microRNA
ERCP
biomarker
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Royal Surrey County Hospital NHS Foundation Trust
name: Royal Free Hospital NHS Foundation Trust
First posted: 2024-02-14
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients (\>18 years old) undergoing ERCP for benign and malignant pancreatico-biliary disease/strictures.

Brief summary: pancreatic or biliary-tract cancer can be a serious diagnosis, as many patients present too late for surgery. Cancer cells have been found to release small messenger molecules called that regulate cancer genes called microRNAs (miRNAs).

The goal of this observational study is to learn about the role of miRNAs from bile and blood samples in patients with pancreatic cancer and bile duct cancer. The main question\[s\] it aims to answer are:

* Can this detect patients presenting with jaundice (yellow-skin) undergoing endoscopy?
* Can this distinguish between the types of cancer? Participants will have blood and bile samples collected prior to diagnosis and their clinical pathway will be followed up for 6 months.

Detailed description: Biliary strictures may be benign or malignant. The major aetiology of a malignant biliary stricture includes a primary tumour or local extension, such as cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC). There is still ongoing debate about adequate diagnostics in bile duct strictures of unknown aetiology. The application of endoscopic retrograde cholangio-pancreatography (ERCP) is considered to be an essential tool in bile duct strictures. The advantage of ERCP is the ability to achieve biliary decompression and take transpapillary specimens for histological or cytological analysis at the same time. Unfortunately, biliary brush cytology and/or biopsies are often insensitive at detecting malignancy, especially PDAC. MicroRNAs (miRNAs) are newly recognised, small pieces of genetic code that are crucial for regulating cancer genes. It has been previously shown that miRNA "signatures" in tissue and biofluids can be used to detect and prognosticate PDAC. Bile is potentially a rich source of novel biomarkers for PDAC and BTC due to its intimate proximity to the malignant lesion.

This prospective, non-randomised, observational, single-blinded study will investigate, as its primary endpoint, whether candidate biliary miRNAs can differentiate between benign and malignant pancreaticobiliary disease/strictures in patients undergoing ERCP. In order to also generate hypotheses, this study also has several exploratory endpoints for translational research. This will focus on patients with presenting with PDAC, correlating miRNA levels with clinicopathologic factors and survival outcomes, in order to establish bile miRNAs as predictive and prognostic biomarkers. Moreover, the study will aim to elucidate the molecular mechanisms and source of the dysregulated biliary miRNAs in PDAC.

In summary, there is currently no effective method to differentiate malignant from benign biliary strictures, or the ability to stratify these tumours pre-operatively based on their biological subtype and aggressiveness. The proposed study aims to improve the speed and accuracy of diagnosing these tumours by using measuring bile-based miRNA signatures. Importantly, it has been shown that biliary miRNAs can be easily extracted and analysed, and these molecules are stable in clinical settings. The development of clinically useful biliary miRNA biomarkers will result in considerable patient benefits.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Scheduled for clinical reason to undergo an ERCP (endoscopic retrograde cholangiopancreatography).
* WHO performance status 0, 1 or 2.
* Willing and mentally able to provide written informed consent.
* Suspected of having benign pancreaticobiliary disease (e.g. chronic pancreatitis, primary sclerosing cholangitis, common bile duct gallstones (choledocholithiasis), sphincter of Oddi dysfunction); or suspected of having PDAC or BTC.
* Presenting with obstructive jaundice and/or an indeterminate biliary stricture.

Exclusion Criteria:

* Age \<18years old.
* Patients undergoing ERCP post-bariatric surgery, hepatico-jejunostomy or Bilroth II .
* Pregnancy.
* WHO performance status 3 or 4.
* Not willing or able to sign informed consent.
* Not scheduled for endoscopic procedures for clinical reasons.
* No clinical or image data suggestive of pancreaticobiliary disease and need for endoscopic intervention or investigation.

Primary outcomes:
measure: Diagnostic Value as measured by Area under the Curve (AUC) for candidate miRNAs
timeFrame: On the day of ERCP
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Adam E Frampton, MB BS FRCS PhD
role: PRINCIPAL_INVESTIGATOR
References: