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

City of Hope

Status: Enrolling

Conditions: PDAC - Pancreatic Ductal Adenocarcinoma

Treatments: Diagnostic Test: EXELiM small RNA sequencing; Diagnostic Test: EXELiM assay (qRT-PCR validation)

Study type: Observational

Funder types: Other

Identifiers

NCT07224802

19288/FORESIGHT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

400 participants in 6 patient groups

Training Cohort - PDAC with Occult Liver Metastasis

Description:

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).

Treatment:

Diagnostic Test: EXELiM assay (qRT-PCR validation)

Training Cohort - PDAC without Occult Liver Metastasis

Description:

Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the first cohort (training set).

Treatment:

Diagnostic Test: EXELiM assay (qRT-PCR validation)

Validation Cohort - PDAC with Occult Liver Metastasis

Description:

Patients with PDAC who were found to have occult liver metastases (early postoperative hepatic recurrence within 6 months) in the second cohort (validation set).

Treatment:

Diagnostic Test: EXELiM assay (qRT-PCR validation)

Validation Cohort - PDAC without Occult Liver Metastasis

Description:

Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the second cohort (validation set).

Treatment:

Diagnostic Test: EXELiM assay (qRT-PCR validation)

Discovery Cohort - PDAC with Occult Liver Metastasis

Description:

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.

Treatment:

Diagnostic Test: EXELiM small RNA sequencing

Discovery Cohort - PDAC without Occult Liver Metastasis

Description:

Patients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the discovery cohort.

Treatment:

Diagnostic Test: EXELiM small RNA sequencing