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

NCT06957691 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GR1000264
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Prostate Cancer; Prostate Carcinoma; Prostate Cancer (Adenocarcinoma); Prostate Cancer Metastatic Disease; Prostate Cancer Recurrent; Prostate Neoplasm; Prostate Adenocarcinoma; Prostate Cancer With Bone Metastasis; Vasomotor Disturbance; Vasomotor Symptoms; Vasomotor Symptoms (VMS); Vasomotor Symptoms as a Sex Hormone-dependent Disorder in Women and Men; Vasomotor Symptoms; Hot Flashes; Androgen Deprivation Therapy; Androgen Ablative Therapy of Advanced Hormone-dependent Prostate Carcinoma; Androgen-deprivation Therapy; Hot Flashes; Hot Flushes; Hot Flushes and/or Sweats

Keywords

Androgen Deprivation Therapy; Hot Flashes; Hot Flushes; Prostate Cancer; Vasomotor Symptoms

Outcome Measures

Primary Outcomes (2)

• Change in the Frequency of Vasomotor Symptoms Through Daily Hot Flash Diary from Baseline to 4 Weeks

  Participants achieved a response if they had a significant decrease in scores in the hot flash diary.

  From baseline to the end of treatment at 4 weeks.

• Hepatic safety, as assessed by measuring liver function tests

  Fezolinetant was considered safe if liver function tests did not change significantly.

  From baseline to the end of treatment at 4 weeks.

Secondary Outcomes (11)

• Change in quality-of-life symptoms related to hot flashes, as assessed using the Hot Flash-Related Daily Interference Scale

  From baseline to the end of treatment at 4 weeks.

• Change in overall quality of life, as assessed using the Short Form-36 questionnaire

  From baseline to the end of treatment at 4 weeks.

• Change in sleep quality, as assessed using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance questionnaire

  From baseline to the end of treatment at 4 weeks.

• Change in mood, as assessed using the Positive and Negative Affect Schedule questionnaire

  From baseline to the end of treatment at 4 weeks.

• Change in sexual function, as assessed using the Sexual Arousal, Interest and Drive questionnaire

  From baseline to the end of treatment at 4 weeks.

Study Arms (2)

Fezolinetant

EXPERIMENTAL

Daily oral administration at a dose of 45 mg

Drug: fezolinetant - reference formulation

Placebo

PLACEBO COMPARATOR

Daily oral administration

Drug: Placebo

Interventions

fezolinetant - reference formulation DRUG

Daily oral administration of fezolinetant at a dose of 45 mg

Fezolinetant

Placebo DRUG

Daily oral administration of placebo

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male sex
• Age 40 years and older
• Diagnosis of prostate cancer
• Androgen deprivation therapy
• Presence of 5 or more moderate-to-severe hot flashes per day or 35 or more moderate-to-severe hot flashes per week
• Ability to sign the inform consent
• Willing to use reliable methods of contraception if partner is of childbearing age
• Ability to record hot flashes electronically

You may not qualify if:

• Use of abiraterone acetate
• Use of docetaxel and other chemotherapeutic agents
• Liver cirrhosis
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of normal
• Total bilirubin above the upper limit of normal
• Glomerular filtration rate \< 30 mL/min
• Use of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, sedatives, or hypnotics
• Use of over-the-counter hormonal agents or herbal compounds
• Current use of CYP1A2 inhibitors
• Ingestion of alcohol within 2 weeks prior to the baseline visit
• Inability to abstain from alcohol use during the study period.

Sponsors & Collaborators

• Shehzad Basaria, M.D.: lead
• Astellas Pharma US, Inc.: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (18)

• 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.

  PMID: 36734148 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.

  PMID: 36924778 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.

  PMID: 34965909 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.

  PMID: 19758646 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.

  PMID: 17099626 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.

  PMID: 26673756 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.

  PMID: 36633525 BACKGROUND

• Lee A. Fezolinetant: First Approval. Drugs. 2023 Aug;83(12):1137-1141. doi: 10.1007/s40265-023-01917-1.

  PMID: 37462862 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.

  PMID: 1708331 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.

  PMID: 30504731 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.

  PMID: 33724119 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.

  PMID: 28380486 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.

  PMID: 15161582 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.

  PMID: 18231613 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.

  PMID: 16786037 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.

  PMID: 29549104 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.

  PMID: 19901933 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.

  PMID: 16014598 BACKGROUND

Related Links

• Highlights of Prescribing Information. VEOZAH® (fezolinetant) tablets, for oral use. Approval: 2023. Revised: 12/2024

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma; Multiple Endocrine Neoplasia Type 1; Hot Flashes

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Shehzad S Basaria, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth Borwick

CONTACT

617-525-8407; eborwick@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 4, 2025
• Study Start: January 14, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (1)