Triple therapy plus HIFU for high-tumor-burden metastatic hormone-sensitive prostate cancer

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 will try combining androgen deprivation therapy, darolutamide, docetaxel, and targeted transrectal HIFU prostate ablation in men with high‑tumor‑burden metastatic hormone‑sensitive prostate cancer to see if it controls disease and is safe.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Qilu Hospital of Shandong University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07172685 on ClinicalTrials.gov

What this trial studies

This is a single-arm prospective cohort enrolling 116 men with high‑tumor‑burden metastatic hormone‑sensitive prostate cancer who will receive darolutamide, docetaxel, and androgen deprivation therapy combined with transrectal HIFU focal ablation of the prostate. The protocol pairs systemic triple therapy with targeted HIFU to the primary tumor and will monitor safety, PSA response, radiographic progression, and adverse events. Eligible patients include those with newly diagnosed or recurrent ADT‑sensitive disease and either ≥4 bone metastases (with ≥1 outside the pelvis or spine) or visceral metastases, and ECOG 0–1. All treatments and follow‑up are delivered at Qilu Hospital of Shandong University in Jinan, China.

Who should consider this trial

Good fit: Men aged 18 or older with high‑tumor‑burden mHSPC (≥4 bone metastases with ≥1 outside the pelvis or spine, or any visceral metastasis), ADT‑sensitive disease, ECOG 0–1, and who can tolerate HIFU and chemotherapy are the intended participants.

Not a fit: Patients with low‑volume disease, castration‑resistant prostate cancer, poor performance status, major comorbidities, or contraindications to HIFU, docetaxel, or darolutamide are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combined approach could improve disease control and delay progression by treating both systemic disease and the primary prostate tumor, potentially extending survival.

How similar studies have performed: The phase III PEACE‑1 trial showed a survival benefit when adding abiraterone to ADT plus docetaxel, but combining systemic triple therapy with prostate HIFU is a novel approach without established phase‑III evidence.

Eligibility criteria

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.

Where this trial is running

Jinan, Shandong

• Qilu hospital — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Shouzhen Chen, Dr.

Conditions Prostate Cancer