Integrated Cf-miRNA and Exosomal miRNA Signature for Early Detection of Esophageal Squamous Cell Carcinoma (SYNERGY)

December 3, 2025 updated by: City of Hope Medical Center

SYNERGY Study: Early Detection Through Integrated Evaluation of Cell-Free and Exosomal microRNAs for Biomarker-Guided Screening of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) remains a highly lethal cancer worldwide, largely due to late diagnosis. Current screening methods such as upper endoscopy are invasive, operator-dependent, and limited in their ability to detect early-stage lesions.

To address this clinical need, the SYNERGY study seeks to develop a non-invasive, blood-based biomarker assay that integrates cell-free microRNAs (cf-miRNAs) and exosomal microRNAs (exo-miRNAs) to detect ESCC at an early and potentially curable stage.

This multicenter translational study includes discovery, training, and validation phases using preoperative plasma or serum samples. By combining the tumor specificity of exosomal miRNAs with the systemic sensitivity of cf-miRNAs, SYNERGY aims to construct a robust diagnostic model with high sensitivity and specificity for early ESCC detection.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Esophageal cancer is the 11th most common cancer globally and the 7th leading cause of cancer-related death, with an estimated 511,000 new cases and 445,000 deaths annually. ESCC accounts for the majority of cases worldwide. Despite advances in endoscopy and therapy, outcomes for advanced ESCC remain poor, highlighting the pressing need for sensitive, minimally invasive early detection strategies.

Exosomal miRNAs (exo-miRNAs) are selectively released by tumor cells and remain stable in circulation, enabling reliable detection of tumor-specific signals. Cell-free miRNAs (cf-miRNAs) circulate broadly and can reflect overall tumor burden, metastatic spread, and microenvironmental changes.

Previous ESCC biomarker studies were limited by small validation cohorts and reliance on tissue-based public datasets that do not fully capture circulating biomarker patterns. The SYNERGY study addresses these limitations through comprehensive discovery analysis and multi-cohort blood-based validation.

Study Type

Observational

Enrollment (Estimated)

600

Contacts and Locations

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

Study Contact

  • Name: Ajay Goel, PhD
  • Phone Number: 626-218-3452
  • Email: ajgoel@coh.org

Study Locations

  • United States
    • California
      • Monrovia, California, United States, 91016
        • Recruiting
        • City of Hope Medical Center
        • Contact:

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

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients with histologically confirmed ESCC Healthy volunteers or non-disease controls (NDC)

Description

Inclusion Criteria:

  • Adults age 18 to 90 years
  • Histologically confirmed esophageal squamous cell carcinoma
  • No prior systemic therapy before sample collection
  • For control groups: absence of malignant disease

Exclusion Criteria:

  • Lack of informed consent
  • Inadequate sample volume or RNA quality
  • Prior cancer within 5 years (except localized cancers)
  • Active systemic inflammation that may alter circulating RNA profiles

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
Discovery cohort (ESCC)
Patients with ESCC
Diagnostic test: Small RNA sequencing of exo- and cf-miRNAs
Identification of differentially expressed cf-miRNAs
Discovery cohort (NDC)
Non-Disease Control
Diagnostic test: Small RNA sequencing of exo- and cf-miRNAs
Identification of differentially expressed cf-miRNAs
Training cohort (ESCC)
Patients with ESCC
Diagnostic test: PCR-based validation (SYNERGY assay)
PCR-based validation of the SYNERGY miRNA panel
Training cohort (NDC)
Non-Disease Control
Diagnostic test: PCR-based validation (SYNERGY assay)
PCR-based validation of the SYNERGY miRNA panel
Testing cohort (ESCC)
Patients with ESCC
Diagnostic test: RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)
RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier
Testing cohort (NDC)
Non-Disease Control
Diagnostic test: RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)
RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity
Time Frame: At study completion, an average of one year
Comparison of Pathological Diagnosis and the SYNERGY Assay
At study completion, an average of one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC
Time Frame: At Study completion, an average of one year
AUC of integrated cf- + exo-miRNA model
At Study completion, an average of one year
Specificity
Time Frame: Time Frame: At study completion, , an average of one year
Description: Comparison of Pathological Diagnosis and the SYNERGY Assay
Time Frame: At study completion, , an average of one 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)

January 15, 2025

Primary Completion (Estimated)

June 18, 2026

Study Completion (Estimated)

June 18, 2026

Study Registration Dates

First Submitted

November 18, 2025

First Submitted That Met QC Criteria

December 3, 2025

First Posted (Actual)

December 5, 2025

Study Record Updates

Last Update Posted (Actual)

December 5, 2025

Last Update Submitted That Met QC Criteria

December 3, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23228/SYNERGY

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

De-identified participant data will be made available at the time of publication through a signed data access agreement, pending approval by the investigators for proposed scientific use.

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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