Proof-of-Concept Trial to Assess the Efficacy and Safety of Fezolinetant in Improving Vasomotor Symptoms in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy

Summary

The goal of this clinical trial is to learn if fezolinetant can treat hot flashes (vasomotor symptoms) in men with prostate cancer undergoing androgen deprivation therapy. The main questions it aims to answer are: * Does fezolinetant improve the frequency and severity of hot flashes? * Does fezolinetant cause any harm to the liver? * Does fezolinetant improve quality of life, sleep quality, fatigue, mood, sexual function, and metabolic parameters? Researchers will compare how people respond to fezolinetant versus a placebo, which does not contain any active medicine. Participants will: * Take fezolinetant or a placebo every day for 4 weeks * Visit the clinic once every 2 weeks for checkups and tests * Keep a diary of the number of times and intensity that they experience hot flashes

Timeline

Start

2026-01-14

Primary completion

2028-08-31

Completion

2028-12-31

Publications

• Background Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M, Stute P, Thurston RC, Wolfman W, English M, Franklin C, Lee M, Santoro N. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab. 2023 Jul 14;108(8):1981-1997. doi: 10.1210/clinem/dgad058.
• Background Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, English M, Franklin C, Lee M, Neal-Perry G. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102. doi: 10.1016/S0140-6736(23)00085-5. Epub 2023 Mar 13.
• Background Patel B, S Dhillo W. Menopause review: Emerging treatments for menopausal symptoms. Best Pract Res Clin Obstet Gynaecol. 2022 May;81:134-144. doi: 10.1016/j.bpobgyn.2021.10.010. Epub 2021 Nov 17.
• Background Sharma P, Wisniewski A, Braga-Basaria M, Xu X, Yep M, Denmeade S, Dobs AS, DeWeese T, Carducci M, Basaria S. Lack of an effect of high dose isoflavones in men with prostate cancer undergoing androgen deprivation therapy. J Urol. 2009 Nov;182(5):2265-72. doi: 10.1016/j.juro.2009.07.030. Epub 2009 Sep 16.
• Background Harle LK, Maggio M, Shahani S, Braga-Basaria M, Basaria S. Endocrine complications of androgen-deprivation therapy in men with prostate cancer. Clin Adv Hematol Oncol. 2006 Sep;4(9):687-96.
• Background Hunter MS, Stefanopoulou E. Vasomotor symptoms in prostate cancer survivors undergoing androgen deprivation therapy. Climacteric. 2016;19(1):91-7. doi: 10.3109/13697137.2015.1125460. Epub 2015 Dec 16.
• Background Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
• Background Lee A. Fezolinetant: First Approval. Drugs. 2023 Aug;83(12):1137-1141. doi: 10.1007/s40265-023-01917-1.
• Background Rance NE, Young WS 3rd. Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women. Endocrinology. 1991 May;128(5):2239-47. doi: 10.1210/endo-128-5-2239.
• Background Modi M, Dhillo WS. Neurokinin 3 Receptor Antagonism: A Novel Treatment for Menopausal Hot Flushes. Neuroendocrinology. 2019;109(3):242-248. doi: 10.1159/000495889. Epub 2018 Nov 30.
• Background Depypere H, Lademacher C, Siddiqui E, Fraser GL. Fezolinetant in the treatment of vasomotor symptoms associated with menopause. Expert Opin Investig Drugs. 2021 Jul;30(7):681-694. doi: 10.1080/13543784.2021.1893305. Epub 2021 Jul 12.
• Background Skorupskaite K, George JT, Veldhuis JD, Millar RP, Anderson RA. Neurokinin 3 Receptor Antagonism Reveals Roles for Neurokinin B in the Regulation of Gonadotropin Secretion and Hot Flashes in Postmenopausal Women. Neuroendocrinology. 2018;106(2):148-157. doi: 10.1159/000473893. Epub 2017 Apr 5.
• Background Stearns V. Management of hot flashes in breast cancer survivors and men with prostate cancer. Curr Oncol Rep. 2004 Jul;6(4):285-90. doi: 10.1007/s11912-004-0037-y.
• Background Guise TA, Oefelein MG, Eastham JA, Cookson MS, Higano CS, Smith MR. Estrogenic side effects of androgen deprivation therapy. Rev Urol. 2007 Fall;9(4):163-80.
• Background Naoe M, Ogawa Y, Shichijo T, Fuji K, Fukagai T, Yoshida H. Pilot evaluation of selective serotonin reuptake inhibitor antidepressants in hot flash patients under androgen-deprivation therapy for prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(3):275-8. doi: 10.1038/sj.pcan.4500891. Epub 2006 Jun 20.
• Background Russell N, Hoermann R, Cheung AS, Ching M, Zajac JD, Handelsman DJ, Grossmann M. Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial. Eur J Endocrinol. 2018 May;178(5):565-576. doi: 10.1530/EJE-17-1072. Epub 2018 Mar 16.
• Background Freedland SJ, Eastham J, Shore N. Androgen deprivation therapy and estrogen deficiency induced adverse effects in the treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2009;12(4):333-8. doi: 10.1038/pcan.2009.35. Epub 2009 Sep 1.
• Background Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005 Jul 13;294(2):238-44. doi: 10.1001/jama.294.2.238.

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