Study on Triple Therapy Combined With HIFU for High-Tumor-Burden mHSPC

September 7, 2025 updated by: Qilu Hospital of Shandong University

Exploratory Study on the Efficacy and Safety of Triple Therapy (ADT + Darolutamide + Docetaxel Chemotherapy) Combined With Transrectal High-Intensity Focused Ultrasound Focal Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) With High Tumor Burden

This study is a single-arm prospective cohort study designed to evaluate the efficacy and safety of triple therapy (ADT + darolutamide + docetaxel) combined with transrectal high-intensity focused ultrasound (HIFU) focal therapy in patients with high-tumor-burden metastatic hormone-sensitive prostate cancer (mHSPC).

A total of 116 high-tumor-burden mHSPC patients will be enrolled and are scheduled to receive the following treatment:

Darolutamide + Docetaxel + ADT + Transrectal HIFU Focal Therapy for the Prostate.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Prostate cancer ranked as the second most commonly diagnosed cancer and the fifth leading cause of cancer death among men worldwide in 2020, with approximately 1.4 million new cases and 375,000 deaths. In China, both the incidence and mortality rates of prostate cancer have shown a significant upward trend.

For prostate cancer treatment, effective management of high-tumor-burden metastatic hormone-sensitive prostate cancer (mHSPC) is crucial for delaying disease progression and improving long-term survival, representing one of the most critical clinical challenges. Although androgen deprivation therapy (ADT) combined with docetaxel or novel hormonal therapy has been established as standard treatment in both domestic and international guidelines, the clinical adoption of these novel ADT-based combination regimens remains limited due to the risk of adverse events (AEs) associated with chemotherapy and prolonged hormone exposure.

Recent advances in mHSPC treatment have brought new hope. The phase III PEACE-1 trial demonstrated that adding abiraterone to standard ADT plus docetaxel significantly reduced mortality risk (median overall survival not reached vs. 4.4 years; HR, 0.75; 95% CI, 0.59-0.96; P=0.021).

SonaCare Medical's Sonablate HIFU system is a global leader in high-intensity focused ultrasound technology, being the first prostate tissue ablation device to receive FDA 510(k) clearance. On July 8, 2020, the Sonablate device obtained approval from China's National Medical Products Administration (NMPA Approval No. 20203010342) for treating both prostate cancer and benign prostatic hyperplasia.

Therefore, this project proposes a single-arm clinical study. From 2022 to 2025, eligible high-tumor-burden mHSPC patients will be enrolled after providing informed consent and baseline data collection. Participants will receive either:

  • Apalutamide + docetaxel + ADT, or
  • Apalutamide + ADT combined with transrectal high-intensity focused ultrasound (HIFU) focal therapy The primary endpoint is 3-year radiographic progression-free survival (rPFS) rate. Follow-up assessments will be conducted per protocol to evaluate efficacy and safety outcomes. This study aims to provide new therapeutic possibilities for high-tumor-burden mHSPC through combination therapy, potentially improving patient prognosis and reducing disease burden.

Study Type

Interventional

Enrollment (Estimated)

116

Phase

  • Not Applicable

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

Study Locations

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

No

Description

Inclusion Criteria:

  1. Patients who agree to participate in the study and sign the informed consent form.
  2. Age ≥18 years, male.
  3. Histologically or cytologically confirmed prostate adenocarcinoma.
  4. Bone scan, CT, or MRI showing ≥4 bone metastases (with ≥1 outside the pelvis or spine) or visceral metastases.
  5. Newly diagnosed or recurrent disease after local therapy, with sensitivity to androgen deprivation therapy (ADT).
  6. Patients who have received ADT (medical or surgical castration) with or without first-generation antiandrogens for ≤3 months, without evidence of soft tissue disease progression (per RECIST 1.1) or clinically significant PSA progression (≥50% increase from nadir with serum testosterone at castrate levels).
  7. Planned treatment with docetaxel plus apalutamide and ADT, or apalutamide plus ADT.
  8. ECOG Performance Status (PS) score of 0-1.

  9. Adequate hematologic and organ function:

    • **Bone marrow function (without transfusion or growth factor support):**
    • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/μL)
    • Hemoglobin ≥90 g/L (9.0 g/dL)
    • Platelet count ≥100 × 10⁹/L (100,000/μL)
    • **Liver function:**
    • Total bilirubin (TBIL) ≤1.5 × ULN
    • AST, ALT, and alkaline phosphatase (ALP) ≤2.5 × ULN
    • **Renal function:**
    • Serum creatinine ≤1.5 × ULN **or** calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault formula)
    • **Coagulation function (without anticoagulation therapy):** INR ≤1.5
  10. Patients of reproductive potential must use effective contraception during the study and for 6 months after the last dose.

Exclusion Criteria:

  1. Lesions located at the prostate apex or in areas inaccessible for focal therapy.
  2. Beaded prostatic calculi or cysts >1 cm in diameter within the treatment or ultrasound pathway.
  3. Urethral stricture or presence of metal/other implants in the urethra.
  4. Prior rectal surgery.
  5. History of or existing rectal fistula.
  6. Rectal stenosis preventing transrectal ultrasound.
  7. Rectal invasion.
  8. Active severe urinary tract infection.
  9. Severe cardiovascular or cerebrovascular disease affecting anesthesia/surgery.
  10. History of hypersensitivity or intolerance to any study drugs.
  11. Planned concurrent anticancer therapy during the study.
  12. Prior treatment with second-generation androgen receptor (AR) inhibitors (e.g., apalutamide, enzalutamide, darolutamide), CYP17 inhibitors (e.g., abiraterone acetate, ketoconazole), chemotherapy, immunotherapy, or adjuvant/neoadjuvant therapy.
  13. Use of herbal products with anti-prostate cancer or PSA-lowering effects (e.g., saw palmetto) within 4 weeks before study treatment.
  14. History of seizures, medications that lower seizure threshold, or conditions predisposing to seizures within 12 months (including TIA, stroke, or traumatic brain injury with hospitalization).
  15. Active cardiac disease within 6 months before treatment: severe/unstable angina, myocardial infarction, congestive heart failure (NYHA Class III/IV), or arrhythmia requiring medication.
  16. Conditions impairing drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction).
  17. Immunodeficiency (e.g., HIV-positive, congenital/acquired immunodeficiency) or organ transplant history.
  18. Known brain metastases.
  19. Other malignancies within 5 years (except cured basal cell carcinoma or cervical carcinoma in situ).
  20. Concurrent participation in another investigational drug/device trial.
  21. Poor compliance likely to hinder treatment/follow-up.
  22. Uncontrolled comorbidities (e.g., hypertension, diabetes, neuropsychiatric disorders) that may compromise safety or confound results, per investigator judgment.
  23. Any other condition deemed unsuitable for inclusion by the investigator.

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Arm
The study plans to enroll 116 patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who will receive the following treatment regimen: Darolutamide , Docetaxel , ADT and transrectal high-intensity focused ultrasound (HIFU) focal therapy for the prostate. Patients will receive each drug according to the prescribing information, with dose adjustments based on adverse reactions (as per the prescribing guidelines).
Combination product: Darolutamide , Docetaxel , ADT and Transrectal HIFU Focal Therapy

Darolutamide , Docetaxel , ADT and Transrectal HIFU Focal Therapy Group:

Darolutamide (600 mg, orally, twice daily) GnRHa (Goserelin 10.8 mg sustained-release implant, subcutaneous injection, every 3 months) Docetaxel (75 mg/m², intravenous infusion, every 3 weeks, for 6 cycles) Dexamethasone (8 mg, orally, 12/3/1 hour before docetaxel infusion)* Prednisone/Prednisolone (at the investigator's discretion)* Transrectal High-Intensity Focused Ultrasound (HIFU) for prostate focal therapy (ablation extent determined based on MRI and biopsy findings; number of treatments ≤ 2)

*Note: Dexamethasone and prednisone/prednisolone are adjunct medications and are not assigned as separate intervention arms; urinary catheter placement is a procedural detail and not listed as an intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA Evaluation
Time Frame: PSA Response Rate at Week 12
Time to PSA Progression
PSA Response Rate at Week 12

Secondary Outcome Measures

Outcome Measure
Time Frame
PFS
Time Frame: Time from randomization to tumor progression (any aspect) or death (any cause), or until a maximum of 2 years of drug exposure per subject, whichever occurs first.
Time from randomization to tumor progression (any aspect) or death (any cause), or until a maximum of 2 years of drug exposure per subject, whichever occurs first.
PSA ≤0.2 ng/ml Response Rate
Time Frame: Months 3, 6, and 12
Months 3, 6, and 12
PSA50 and PSA90 Response Rates
Time Frame: Month 6
Month 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Qilu Hospital of Shandong University

Investigators

  • Study Chair: Shouzhen Chen, Dr., Qilu Hospital of Shandong University

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)

July 30, 2025

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

August 26, 2025

First Submitted That Met QC Criteria

September 7, 2025

First Posted (Estimated)

September 15, 2025

Study Record Updates

Last Update Posted (Estimated)

September 15, 2025

Last Update Submitted That Met QC Criteria

September 7, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSZ04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

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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