Plasma Exosomal RNA Signature for Prostate Cancer Bone Metastasis

NCT07553754 | Recruiting

• 1 other identifier: KY20262011-F-1
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 9

Brief Summary

Brief Summary: This prospective, multicenter study aims to discover, develop, and validate a plasma exosomal RNA-based signature as a rule-out test for predicting bone metastasis in prostate cancer, using baseline treatment-naïve PSMA PET as the gold standard. The study is designed in four sequential phases: Phase 1 (Discovery, n=250): High-throughput sequencing of plasma exosomal RNAs to identify differentially expressed candidate RNAs. Phase 2 (Model Development, n=300): Digital droplet PCR (ddPCR) analysis of candidates in an independent cohort to construct and lock the final multi-RNA predictive signature using appropriate machine learning methods. Phase 3 (Internal Validation, n=300): Independent validation of the locked signature in a consecutive cohort reflecting natural disease prevalence. Phase 4 (External Validation, n=150): Final independent validation in a multi-center cohort enriched for bone metastasis. Primary Outcome: To evaluate the diagnostic performance of the signature as a rule-out test for PSMA PET-defined bone metastasis. The primary performance metrics are: Sensitivity, with a prespecified target of ≥95% (to ensure minimal false negatives). Specificity at the threshold that achieves the ≥95% sensitivity. A specificity of ≥30% will be considered supportive of clinical utility. A specificity of ≥30% (or a lower bound of the 95% confidence interval exceeding 20%) will be considered supportive of clinical utility. Need: Current biomarkers lack sensitivity and specificity for early detection of bone metastasis. More importantly, existing tools lack adequate negative predictive value to safely rule out bone metastasis in low-risk patients, leading to over-imaging or delayed detection. There is an urgent need for a non-invasive rule-out test to safely defer PSMA PET/CT in very-low-risk patients. Plasma exosomal RNAs offer a promising liquid biopsy approach, but prospective multicenter studies with rigorous validation are lacking. Secondary Outcomes:

1. 1.Secondary metrics include negative predictive value (NPV), positive predictive value (PPV), area under the ROC curve (AUC), calibration, and decision curve analysis.
2. 2.Correlation between exosomal RNA levels and number of bone metastatic lesions (PSMA PET).
3. 3.Association with PSA, PSMA PET SUVmax, and MRI findings.
4. 4.Tissue-plasma correlation to confirm tumor origin (exploratory).
5. 5.Mechanistic exploration of key candidates via in vitro/in vivo assays (exploratory).
6. 6.Subgroup analyses by hormone sensitivity, metastatic pattern, Gleason grade (exploratory).
7. 7.Histologically confirmed prostate cancer scheduled for baseline PSMA PET.
8. 8.PSMA PET performed prior to any prostate cancer-related treatment.
9. 9.Blood samples collected prior to any treatment AND prior to prostate biopsy.
10. 10.Willing to undergo prostate biopsy if clinically indicated (after blood collection).
11. 11.Written informed consent.
12. 12.Age ≥18 years.
13. 13.Any prior prostate cancer treatment before baseline PSMA PET.
14. 14.Blood samples collected after prostate biopsy.
15. 15.Other active malignancy within past two years (excluding non-melanoma skin cancer).
16. 16.Inadequate blood sample quality or quantity.
17. 17.Severe comorbidities interfering with study conduct.

Conditions

Bone Metastasis; PSMA PET; Liquid Biopsy; Exosomal RNA; Biomarker Discovery and Validation; Treament-naive; Prostate Cancer (Diagnosis)

Keywords

Prostate Cancer; Bone Metastasis; PSMA PET; Liquid Biopsy; Exosomal RNA; Predictive Signature

Outcome Measures

Primary Outcomes (1)

• Specificity of the plasma exosomal RNA-based predictive signature for detecting PSMA PET-defined bone metastasis at a prespecified sensitivity threshold of ≥95%

  Description: The signature will be developed as a continuous risk score using machine learning in an independent development cohort (Phase 2, n≥300, enriched for bone metastasis). After locking the model, a single cut-off value will be selected in the internal validation cohort (Phase 3, n≥300, reflecting natural disease prevalence) to achieve a sensitivity of ≥95% for detecting PSMA PET/CT-defined bone metastasis. The primary outcome is the specificity of the signature at that cut-off. A specificity of ≥30% (or a lower bound of the 95% confidence interval exceeding 20%) will be considered supportive of clinical utility. Measurement tools and units: Plasma exosomal RNA level: digital droplet PCR (ddPCR), expressed as absolute copy number per mL of plasma. Bone metastasis status: PSMA PET/CT, binary (positive/negative). Sensitivity and specificity: proportions with 95% confidence intervals (Clopper-Pearson exact method).

  Baseline

Secondary Outcomes (7)

• Correlation between plasma exosomal RNA level and bone metastatic lesion count on PSMA PET

  Baseline

• Correlation between plasma exosomal RNA level and serum PSA level

  Baseline

• Correlation between plasma exosomal RNA level and PSMA PET SUVmax

  Baseline

• Association between exo-RNA and MRI findings (exploratory)

  Baseline

• Correlation between tissue RNA expression (RNA-seq, normalized counts like FPKM/TPM) and plasma exosomal RNA level (ddPCR, copies/mL)

  Baseline

Study Arms (1)

Prostate Cancer Cohort

A single cohort of 1000 patients with suspected or histologically confirmed prostate cancer who undergo baseline treatment-naïve PSMA PET imaging. All patients provide blood samples for plasma exosomal RNA analysis, collected prior to any treatment and prior to prostate biopsy. This cohort is used for a four-phase biomarker study: Phase 1 (Discovery, n=250) for RNA sequencing to identify candidate biomarkers; Phase 2 (Model Development, n=300) for digital PCR-based signature development; Phase 3 (Internal Validation, n=300) for independent validation in a consecutive cohort; and Phase 4 (External Validation, n=150) for multi-center validation. Bone metastasis status is defined by PSMA PET. Phase 2 and Phase 3 cohorts are temporally and geographically independent. No patient is included in more than one phase

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study enrolls a total of approximately 1000 patients with histologically confirmed prostate cancer from multiple centers. All patients undergo baseline PSMA PET/CT and provide pre-treatment blood samples (collected before any therapy and before prostate biopsy). The single overall cohort is allocated into four sequential, independent phases: Phase 1 (Discovery, n=250), Phase 2 (Model Development, n≥300, bone-metastasis enriched), Phase 3 (Internal Validation, n≥300, natural prevalence), and Phase 4 (External Validation, n=150, multi-center enriched). Bone metastasis status is defined by PSMA PET/CT.

You may qualify if:

• Patients with histologically confirmed prostate cancer who are scheduled to undergo baseline PSMA PET imaging.
• Patients who undergo PSMA PET imaging prior to any prostate cancer-related treatment (including androgen deprivation therapy, radiotherapy, or surgery).
• Patients who provide blood samples for plasma exosomal RNA analysis collected prior to any treatment AND prior to prostate biopsy (if applicable).
• Whole blood samples (approximately 10 mL) will be collected in EDTA tubes at this specified time point. Samples will be processed within 2 hours to obtain plasma and stored at -80°C until analysis.This timing ensures circulating exosomal RNA profiles reflect tumor biology without biopsy-induced contamination.
• Patients who are willing to undergo prostate biopsy if clinically indicated (biopsy performed after blood collection).
• Patients who provide written informed consent to participate in the study.
• Age ≥18 years.

You may not qualify if:

• Patients who have received any prior prostate cancer-related treatment before the baseline PSMA PET scan (including hormonal therapy, radiotherapy, chemotherapy, or surgery).
• Patients whose blood samples were collected after prostate biopsy.
• Patients with a history of other active malignancies within the past two years (excluding non-melanoma skin cancer).
• Patients with inadequate blood sample quality or quantity for exosomal RNA extraction and analysis (e.g., hemolysis, insufficient volume \<8 mL).
• Patients with severe comorbidities or conditions that, in the judgment of the investigator, could interfere with study compliance or pose significant risk.

Sponsors & Collaborators

• Xijing Hospital: lead
• Air Force Military Medical University, China: collaborator
• Shaanxi Provincial People's Hospital: collaborator
• Yan'an University Affiliated Hospital: collaborator
• Weinan Central Hospital: collaborator
• LanZhou University: collaborator
• Qinghai University: collaborator
• General Hospital of Ningxia Medical University: collaborator
• The Second Affiliated Hospital of Shaanxi University of Chinese Medicine: collaborator

Study Sites (9)

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

RECRUITING

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

RECRUITING

Weinan Central Hospital

Weinan, Shaanxi, China

RECRUITING

Xijing Hospital

Xi'an, Shaanxi, 710032, China

RECRUITING

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, China

RECRUITING

Xijing 986 Hospital

Xi'an, Shaanxi, China

RECRUITING

The Second Affiliated Hospital of Shaanxi University of Chinese Medicine

Xianyang, Shaanxi, China

RECRUITING

Qinghai University Affiliated Hospital

Xining, Shaanxi, China

RECRUITING

Affiliated Hospital of Yan'an University

Yan’an, Shaanxi, China

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Disease

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jianhua Jiao, MD.

CONTACT

+86 18700919857; 1531769428@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: April 28, 2026
• Study Start: March 12, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)