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

NCT07172685 | Recruiting

• 1 other identifier: CSZ04
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• PSA Evaluation

  Time to PSA Progression

  PSA Response Rate at Week 12

Secondary Outcomes (3)

• PFS

  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

  Months 3, 6, and 12

• PSA50 and PSA90 Response Rates

  Month 6

Study Arms (1)

Experimental Arm

EXPERIMENTAL

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

Interventions

Darolutamide , Docetaxel , ADT and Transrectal HIFU Focal Therapy COMBINATION_PRODUCT

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.

Experimental Arm

Eligibility Criteria

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

You may qualify if:

• Patients who agree to participate in the study and sign the informed consent form.
• Age ≥18 years, male.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Bone scan, CT, or MRI showing ≥4 bone metastases (with ≥1 outside the pelvis or spine) or visceral metastases.
• Newly diagnosed or recurrent disease after local therapy, with sensitivity to androgen deprivation therapy (ADT).
• 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).
• Planned treatment with docetaxel plus apalutamide and ADT, or apalutamide plus ADT.
• ECOG Performance Status (PS) score of 0-1.
• 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

You may not qualify if:

• Lesions located at the prostate apex or in areas inaccessible for focal therapy.
• Beaded prostatic calculi or cysts \>1 cm in diameter within the treatment or ultrasound pathway.
• Urethral stricture or presence of metal/other implants in the urethra.
• Prior rectal surgery.
• History of or existing rectal fistula.
• Rectal stenosis preventing transrectal ultrasound.
• Rectal invasion.
• Active severe urinary tract infection.
• Severe cardiovascular or cerebrovascular disease affecting anesthesia/surgery.
• History of hypersensitivity or intolerance to any study drugs.
• Planned concurrent anticancer therapy during the study.
• 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.
• Use of herbal products with anti-prostate cancer or PSA-lowering effects (e.g., saw palmetto) within 4 weeks before study treatment.
• 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).
• Active cardiac disease within 6 months before treatment: severe/unstable angina, myocardial infarction, congestive heart failure (NYHA Class III/IV), or arrhythmia requiring medication.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu hospital

Jinan, Shandong, 276600, China

RECRUITING

Related Publications (13)

• Morris MJ, Rathkopf DE, Novotny W, Gibbons JA, Peterson AC, Khondker Z, Ouatas T, Scher HI, Fleming MT. Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2016 Aug 1;22(15):3774-81. doi: 10.1158/1078-0432.CCR-15-2638. Epub 2016 Feb 8.

  PMID: 26858312 BACKGROUND

• Gan L, Chen S, Wang Y, Watahiki A, Bohrer L, Sun Z, Wang Y, Huang H. Inhibition of the androgen receptor as a novel mechanism of taxol chemotherapy in prostate cancer. Cancer Res. 2009 Nov 1;69(21):8386-94. doi: 10.1158/0008-5472.CAN-09-1504. Epub 2009 Oct 13.

  PMID: 19826044 BACKGROUND

• Darshan MS, Loftus MS, Thadani-Mulero M, Levy BP, Escuin D, Zhou XK, Gjyrezi A, Chanel-Vos C, Shen R, Tagawa ST, Bander NH, Nanus DM, Giannakakou P. Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res. 2011 Sep 15;71(18):6019-29. doi: 10.1158/0008-5472.CAN-11-1417. Epub 2011 Jul 28.

  PMID: 21799031 BACKGROUND

• Zhu Y, Liu C, Armstrong C, Lou W, Sandher A, Gao AC. Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer. Clin Cancer Res. 2015 Sep 15;21(18):4133-42. doi: 10.1158/1078-0432.CCR-15-0269. Epub 2015 May 20.

  PMID: 25995342 BACKGROUND

• Galletti G, Matov A, Beltran H, Fontugne J, Miguel Mosquera J, Cheung C, MacDonald TY, Sung M, O'Toole S, Kench JG, Suk Chae S, Kimovski D, Tagawa ST, Nanus DM, Rubin MA, Horvath LG, Giannakakou P, Rickman DS. ERG induces taxane resistance in castration-resistant prostate cancer. Nat Commun. 2014 Nov 25;5:5548. doi: 10.1038/ncomms6548.

  PMID: 25420520 BACKGROUND

• Eigl BJ, Eggener SE, Baybik J, Ettinger S, Chi KN, Nelson C, Wang Z, Gleave ME. Timing is everything: preclinical evidence supporting simultaneous rather than sequential chemohormonal therapy for prostate cancer. Clin Cancer Res. 2005 Jul 1;11(13):4905-11. doi: 10.1158/1078-0432.CCR-04-2140.

  PMID: 16000589 BACKGROUND

• Ueda Y, Matsubara N, Takizawa I, Nishiyama T, Tabata K, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H. A multicenter retrospective analysis of sequential treatment of abiraterone acetate followed by docetaxel in Japanese patients with metastatic castration-resistant prostate cancer. Jpn J Clin Oncol. 2015 Aug;45(8):774-9. doi: 10.1093/jjco/hyv070. Epub 2015 May 15.

  PMID: 25981621 BACKGROUND

• Zhang T, Dhawan MS, Healy P, George DJ, Harrison MR, Oldan J, Chin B, Armstrong AJ. Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer. 2015 Aug;13(4):392-399. doi: 10.1016/j.clgc.2015.01.004. Epub 2015 Jan 24.

  PMID: 25708161 BACKGROUND

• Mezynski J, Pezaro C, Bianchini D, Zivi A, Sandhu S, Thompson E, Hunt J, Sheridan E, Baikady B, Sarvadikar A, Maier G, Reid AHM, Mulick Cassidy A, Olmos D, Attard G, de Bono J. Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Ann Oncol. 2012 Nov;23(11):2943-2947. doi: 10.1093/annonc/mds119. Epub 2012 Jul 5.

  PMID: 22771826 BACKGROUND

• de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, Baron B, Hirmand M, Werbrouck P, Fizazi K. Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for >/=24 weeks in Europe. Eur Urol. 2018 Jul;74(1):37-45. doi: 10.1016/j.eururo.2017.07.035. Epub 2017 Aug 23.

  PMID: 28844372 BACKGROUND

• Matsubara N, Yamada Y, Tabata KI, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H, Yano A, Kawakami S, Otsuka M, Fukasawa S. Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2018 Apr;16(2):142-148. doi: 10.1016/j.clgc.2017.09.008. Epub 2017 Sep 23.

  PMID: 29042308 BACKGROUND

• Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J, Zulfiqar M, Sunderland K, Azad AA, Kollmannsberger CK, Eigl BJ, Noonan K, Wadhwa D, Attwell A, Keith B, Ellard SL, Le L, Gleave ME, Wyatt AW, Chi KN. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol. 2019 Dec;20(12):1730-1739. doi: 10.1016/S1470-2045(19)30688-6. Epub 2019 Nov 11.

  PMID: 31727538 BACKGROUND

• McGuire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016 Mar 15;7(2):418-9. doi: 10.3945/an.116.012211. Print 2016 Mar. No abstract available.

  PMID: 26980827 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Docetaxel; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Shouzhen Chen, Dr.

  Qilu Hospital of Shandong University

  STUDY CHAIR

Central Study Contacts

Shouzhen Chen, Dr.

CONTACT

18560089085; chensz@mail.sdu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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-volume metastatic hormone-sensitive prostate cancer (mHSPC).

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 15, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)