NCT07224802

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

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 372 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• PDAC - Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2024-06-21
• Primary completion: 2026-01-18
• Completion: 2026-02-18
• First posted: 2025-11-05
• Last updated: 2026-03-13

Locations

1 site across 1 country: United States