Forecasting Occult liveR Metastasis Using an Exosomal Signature for Intelligent Guided Hepatic Targeting (FORESIGHT)

March 11, 2026 updated by: City of Hope Medical Center

An Exosome-based Liquid Biopsy Signature for Preoperative Identification of Occult Liver Metastasis in Patients With Pancreatic Ductal Adenocarcinoma

Early liver metastasis (Early-LiM) is the most significant prognostic factor in pancreatic ductal adenocarcinoma (PDAC) and is thought to originate from occult micrometastases present at the time of surgery. Reliable preoperative detection of such lesions remains an unmet clinical need.

The EXELiM study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to accurately identify PDAC patients at high risk of occult liver metastasis before surgery. By integrating machine learning with multi-institutional plasma exosome profiling, this study seeks to enable biology-driven patient stratification and guide treatment sequencing toward precision oncology.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies, with a 5-year overall survival rate below 10%. Even after curative-intent pancreatectomy, over 70% of patients experience disease recurrence, with early liver metastasis (within six months postoperatively) representing the most aggressive and fatal pattern.

Emerging evidence indicates that pancreatic tumors release exosomes that modulate the liver microenvironment, establishing a premetastatic niche that facilitates early colonization. We hypothesize that circulating exosomal microRNAs reflect these biological processes and can serve as non-invasive biomarkers for detecting occult liver metastasis.

In this multi-center observational study, preoperative plasma-derived exosomes from PDAC patients are analyzed using next-generation small RNA sequencing and validated by RT-qPCR. A machine learning model is employed to integrate exo-miRNA expression profiles and clinical variables, yielding a predictive score for early liver metastasis risk.

The study evaluates the diagnostic accuracy, prognostic utility, and clinical benefit of the exo-miRNA panel compared to conventional biomarkers such as CA19-9.

Study Type

Observational

Enrollment (Actual)

372

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91016
        • City of Hope Medical Center

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

Patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC) who have undergone curative-intent pancreatectomy with available preoperative plasma samples.

Description

Inclusion Criteria:

  • Histologically confirmed pancreatic ductal adenocarcinoma (PDAC)
  • Undergoing curative-intent pancreatectomy
  • Availability of preoperative plasma samples
  • Complete clinical and follow-up data
  • Written informed consent obtained

Exclusion Criteria:

  • Synchronous or secondary malignancies
  • Non-adenocarcinoma histology
  • Lack of informed consent
  • Incomplete plasma sample data

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
Training Cohort - PDAC with Occult Liver Metastasis
Patients with PDAC who were found to have occult liver metastases at the time of or shortly after curative-intent pancreatectomy (within 6 months post-surgery), in the first cohort (training set).
Diagnostic test: EXELiM assay (qRT-PCR validation)

Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts.

Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.
Training Cohort - PDAC without Occult Liver Metastasis
Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the first cohort (training set).
Diagnostic test: EXELiM assay (qRT-PCR validation)

Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts.

Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.
Validation Cohort - PDAC with Occult Liver Metastasis
Patients with PDAC who were found to have occult liver metastases (early postoperative hepatic recurrence within 6 months) in the second cohort (validation set).
Diagnostic test: EXELiM assay (qRT-PCR validation)

Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts.

Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.
Validation Cohort - PDAC without Occult Liver Metastasis
Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the second cohort (validation set).
Diagnostic test: EXELiM assay (qRT-PCR validation)

Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts.

Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.
Discovery Cohort - PDAC with Occult Liver Metastasis
Patients with PDAC who were found to have occult liver metastases at the time of or shortly after curative-intent pancreatectomy (within 6 months post-surgery), in the discovery cohort.
Diagnostic test: EXELiM small RNA sequencing
High-throughput small RNA sequencing performed on preoperative plasma samples from PDAC patients in the discovery cohort to identify exosome-derived microRNAs associated with occult liver metastasis or early postoperative hepatic recurrence.
Discovery Cohort - PDAC without Occult Liver Metastasis
Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the discovery cohort.
Diagnostic test: EXELiM small RNA sequencing
High-throughput small RNA sequencing performed on preoperative plasma samples from PDAC patients in the discovery cohort to identify exosome-derived microRNAs associated with occult liver metastasis or early postoperative hepatic recurrence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specificity
Time Frame: Through study completion, an average of 3 year
True Negative Rate: probability of a negative test result conditioned on absence of early liver metastasis
Through study completion, an average of 3 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity
Time Frame: Through study completion, an average of 3 year
True Positive Rate: probability of a positive test result conditioned on the presence of early liver metastasis
Through study completion, an average of 3 year
Area Under the Receiver Operating Characteristic Curve (AUC)
Time Frame: Through study completion, an average of 3 year
Description: AUC representing the overall discriminative ability of the circRNA-based model.
Through study completion, an average of 3 year

Collaborators and Investigators

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

Sponsor

City of Hope Medical Center

Investigators

  • Principal Investigator: Ajay Goel, PhD, City of Hope Medical Center

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

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 (Actual)

June 21, 2024

Primary Completion (Actual)

January 18, 2026

Study Completion (Actual)

February 18, 2026

Study Registration Dates

First Submitted

November 3, 2025

First Submitted That Met QC Criteria

November 3, 2025

First Posted (Actual)

November 5, 2025

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 19288/FORESIGHT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

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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