Molecular Subtyping of Breast Cancer-derived Small Extracellular Vesicles (sEVs) to Predict Therapeutic Efficacy

Molecular Subtyping of Breast Cancer-derived Small Extracellular Vesicles (sEVs) to Predict Therapeutic Efficacy: An Exploratory, Single-Center, Phase II Clinical Study

The goal of this observational study is to learn if a new diagnostic test using specific labels for breast cancer sEVs on a microchip can accurately diagnose the molecular subtypes in patients with breast cancer. The main questions it aims to answer are:

• What is the sensitivity of this new sEVs-based panel for diagnosing breast cancer molecular subtypes?
• What is the specificity of this new sEVs-based panel for diagnosing breast cancer molecular subtypes? Researchers will compare the results from the new sEVs panel to the results from the standard pathological diagnosis to see if the new panel is accurate and reliable.

Participants will be asked to:

• Provide blood samples and tissue samples.
• Allow researchers to access their clinical data, such as their diagnosis, treatment information, and outcomes.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Ting Li
• Study Contact Backup: Name: Xiahong Wang; Phone Number: 8613524491606; Email: whx365@126.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Hongxia wang, PHD; Phone Number: 021-64175590; Email: whx365@126.com
      • Contact: Email: whx365@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Advanced breast cancer

Description

Inclusion Criteria:

1. Age 18-75 years (inclusive)
2. ECOG performance status 0-1
3. Life expectancy ≥3 months
4. Unresectable or metastatic breast cancer
5. Core needle biopsy of recurrent/metastatic lesions is ongoing or planned before initiating new treatment regimen, with provision of fresh tumor tissue specimens and collection of peripheral blood samples
6. Per RECIST v1.1 criteria, at least one measurable lesion or bone-only metastases

7. Adequate bone marrow reserve and organ function prior to first dose:

   • Bone marrow reserve: Platelet count (PLT) ≥90 × 10⁹/L, absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, hemoglobin ≥9 g/dL
   • Coagulation function: INR ≤1.5, APTT ≤1.5 × ULN
   • Hepatic function: Basically normal liver function, total bilirubin ≤1.5 × ULN (patients with Gilbert's syndrome may have total bilirubin ≤3 × ULN), AST and ALT ≤2.5 × ULN (if liver metastases are present, AST and ALT ≤5 × ULN)
   • Renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula)
   • Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%; QTcF ≤470 ms for females, ≤450 ms for males Able to communicate effectively with the investigator and understand and comply with all requirements of the study -

Exclusion Criteria:

1. Receipt of radiotherapy, chemotherapy, traditional Chinese medicine with anti-tumor indications, or local therapy (interventional treatment but excluding tumor biopsy, ablation therapy, etc.) within 2 weeks prior to enrollment
2. Adverse reactions from previous anti-tumor treatment not recovered to ≤Grade 1 per CTCAE v5.0 (except for toxicities judged by the investigator to have no safety risk, such as alopecia, long-term toxicities from radiotherapy, or other toxicities ≤Grade 2)
3. Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin
4. Uncontrolled or serious medical conditions, including but not limited to active infections requiring systemic antibiotic therapy

5. History of serious cardiovascular or cerebrovascular diseases, including but not limited to:

   • Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, etc.
   • Class III-IV cardiac dysfunction per New York Heart Association (NYHA) criteria
   • Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade ≥3 cardiovascular or cerebrovascular events within 6 months prior to first dose
   • Clinically uncontrolled hypertension
   • Any factors that increase the risk of QTc prolongation or arrhythmias, such as heart failure, hypokalemia, congenital long QT syndrome, or use of any concomitant medications known or suspected to prolong the QT interval
6. History of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or history of organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation

7. HIV infection, active HBV or HCV infection; the following situations are allowed for enrollment:

   • Patients positive for hepatitis B surface antigen (HBsAg), with or without positive hepatitis B core antibody (anti-HBc), if HBV DNA <500 IU/mL or below the lower limit of the study site's reference range, and active infection is ruled out by the investigator based on clinical treatment, presentation, etc.
   • Patients positive for hepatitis C (HCV) antibody when HCV RNA is negative
8. Females of childbearing potential with positive pregnancy test within 7 days prior to first dose or who are lactating
9. Known psychiatric illness or disorder that may affect study compliance
10. Other conditions judged by the investigator to be unsuitable for participation in this study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Phase 1（Model Building Cohort）
Phase 1（Model Building Cohort）, Phase 2（External Validation Cohort）; Phase 1（Model Building Cohort）: 500 participants will be enrolled to construct a classifier composed of sEVs molecules as a predictive model for molecular subtyping. Phase 2（External Validation Cohort）: 1,000 participants will be enrolled to evaluate the sensitivity and specificity of sEVs-specific markers for breast cancer molecular subtyping diagnosis compared with classical pathological molecular subtyping diagnosis using ROC curves and other tools. This phase will delineate the distribution of sEVs molecular subtypes and explore the correlation between sEVs molecular subtypes and the efficacy of treatment regimens selected by physicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of sEVs-specific markers for breast cancer molecular subtyping diagnosis	Sensitivity and specificity of sEVs-specific markers for breast cancer molecular subtyping diagnosis	From baseline through treatment completion, up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of sEVs molecular subtypes	Distribution of sEVs molecular subtypes	From baseline through treatment completion, up to 36 months
Correlation analysis between sEVs molecular subtypes and drug efficacy	Correlation analysis between sEVs molecular subtypes and drug efficacy	From baseline through treatment completion, up to 36 months
PFS (Progression-Free Survival)	Time from start of treatment to the first documented disease progression per RECIST v1.1 or death due to any cause.	From treatment initiation until progression or death, up to 36 months
Overall Survival (OS) and Objective Response Rate (ORR)	Objective Response Rate (ORR): As assessed according to the RESIST 1.1 criteria, with complete response (CR) and partial response (PR) combined to define a response. Overall Survival (OS): The time from enrolment to death from any cause; for lost-to-follow-up patients, survival is calculated as of the date of the last follow-up visit, and these are treated as censored data.	From treatment initiation until progression or death , up to 36 months
Safety and Tolerability of Physician-Selected Treatment Regimens	All subjects shall undergo toxicity assessment from the start of their first treatment, with toxicity assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	From treatment initiation until 30 days after the last dose, or until the initiation of a new antineoplastic therapy, whichever occurs first.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: sEVs-ABC-IIT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No