Exosome-derived Extrahepatic Metastasis Detection By Liquid Biopsy In Colorectal Cancer Liver Metastases

NCT ID: NCT07224724

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2026-06-18

Brief Summary

Colorectal cancer is the third most common malignancy worldwide, and prognosis largely depends on how effectively metastatic disease is managed. The liver is the most frequent and prognostically important site of metastasis, and patients responding well to chemotherapy may become candidates for curative hepatic resection. However, the presence of extrahepatic metastasis (EHM) critically influences treatment eligibility and survival. Although clinical scores such as the Fong and Beppu systems include EHM as a determinant, its detection by imaging remains limited, especially for small or occult lesions. Accurate identification of EHM is also essential when considering liver transplantation for unresectable colorectal liver metastases (CRLM), where EHM remains an exclusion criterion.

The EXELION Study aims to develop a non-invasive diagnostic model using serum exosomal microRNAs (miRNAs) to detect both hepatic and extrahepatic metastases in patients with CRLM. By integrating circulating miRNA profiling with machine learning-based analysis, this study seeks to supplement imaging diagnostics, improve treatment stratification, and enhance clinical decision-making for metastatic colorectal cancer.

Detailed Description

Despite improvements in diagnostic imaging-such as CT, MRI, and PET-CT-the sensitivity of EHM detection remains limited, particularly for small or occult lesions in the lung, peritoneum, or lymph nodes. As a result, patients may be inappropriately excluded from curative surgery or exposed to non-beneficial interventions. Thus, there is a pressing need for novel, non-invasive biomarkers capable of detecting EHM with higher accuracy than imaging alone.

MicroRNAs (miRNAs), especially those encapsulated within exosomes, have emerged as stable and reproducible biomarkers reflecting tumor dynamics. Recent studies have shown that circulating miRNA signatures are associated with liver metastasis, therapeutic response, and recurrence risk in CRC. However, their utility for detecting extrahepatic metastasis has not yet been validated in clinical cohorts.

In this research effort, the investigators will leverage small RNA sequencing and machine learning to develop a predictive model for the presence of hepatic and extrahepatic metastases in patients with CRLM. The research plan will consist of three phases:

1. A discovery phase, identifying candidate miRNAs associated with the presence of EHM using next-generation sequencing (NGS) or microarray-based profiling of serum exosomal miRNAs.

2. A model development phase, establishing a quantitative reverse transcription PCR (RT-qPCR) assay and training a predictive algorithm.

3. A validation phase, independently testing the predictive accuracy of the model in an external cohort.

This diagnostic framework is provisionally termed "EXELION" (Exosome-derived Extrahepatic Metastasis Detection by LIquid Biopsy in Colorectal Cancer Liver Metastases). At the end of this study, the EXELION assay is expected to serve as a non-invasive tool to assist clinical decision-making by accurately predicting the presence of extrahepatic metastasis in patients with CRLM.

Conditions

Colorectal Cancer Liver Metastases (CRLM); Metastatic Colorectal Carcinoma (mCRC)

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Extrahepatic liver metastasis patients(Discovery Cohort)

Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.

No interventions assigned to this group

Non-extrahepatic liver metastasis patients(Discovery Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.

EXELION

Intervention Type: OTHER

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Extrahepatic liver metastasis patients(Training Cohort)

Extrahepatic liver metastasis patients (Training Cohort) Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (training) cohort.

EXELION

Intervention Type: OTHER

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Non-extrahepatic liver metastasis patients (Training Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the (training) cohort.

EXELION

Intervention Type: OTHER

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Extrahepatic liver metastasis patients (Validation Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort

No interventions assigned to this group

Non-extrahepatic liver metastasis patients (Validation Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort

EXELION

Intervention Type: OTHER

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Interventions

EXELION

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adults (≥18 years old)
• Histologically- or cytologically-confirmed colorectal cancer that is metastatic
• Availability of pre-treatment plasma samples
• Written informed consent provided
• Sufficient clinical and imaging data to determine presence/absence of extrahepatic metastasis

Exclusion Criteria

• Prior malignancies within 5 years
• Poor sample quality or hemolysis
• Inability to provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajay Goel, PhD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ajay Goel, PhD

Role: CONTACT

AJGOEL@COH.ORG

626-218-3452

Facility Contacts

Ajay Goel, PhD

Role: primary

AJGOEL@COH.ORG

626-218-3452

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Other Identifiers

23228/EXELION

Identifier Type: -

Identifier Source: org_study_id