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

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.

Timeline

Start

2025-07-30

Primary completion

2026-06-30

Completion

2027-06-30

Publications

• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.

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