A Trial on Fezolinetant for Vasomotor Symptoms in Men Receiving Androgen Deprivation Therapy (ADT)

Official title

A Phase II Trial on Fezolinetant for Vasomotor Symptoms in Men Receiving Androgen Deprivation Therapy (ADT) for Prostate Cancer (Fez-Cap)

Overview

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical study to investigates the efficacy of fezolinetant in men undergoing ADT for prostate cancer in alleviating Vasomotor syndromes.

Detailed description

Participants will be randomized in a 1:1 manner to receive fezolinetant 45 mg or placebo orally once daily for 12 weeks in total, with the primary and secondary outcomes being assessed at week 4, 8 and 12 with standardized questionnaires, symptom diaries, blood taking, and clinical history taking in the clinic setting.

Interventions

• Drug Fezolinetant
  Fezolinetant 45 mg orally once daily for 12 weeks.
• Drug Placebo
  Placebo orally once daily for 12 weeks.

Primary outcome measures

• Hot flush severity [Time frame: Baseline, week 3, week 7 and week 11]
• Daily hot flush score [Time frame: Baseline, week 3, week 7 and week 11]

Secondary outcome measures (6)

• Patient reported quality of life by QLQ-C30 [Time frame: Baseline, week 4, week 8 and week 12]
• Sleep Quality [Time frame: Baseline, week 4, week 8 and week 12]
• Mood status [Time frame: Baseline, week 4, week 8 and week 12]
• Lower urinary tract symptoms (LUTS) [Time frame: Baseline, week 4, week 8 and week 12]
• Patient reported quality of life by Hot Flash-Related Daily Interference Scale (HFRDIS) [Time frame: Baseline, week 4, week 8 and week 12]
• Adverse Events [Time frame: Baseline, Week 4, Week 8 and Week 12]

Eligibility criteria

Inclusion criteria

• Patients aged at least 18 years old on the index date
• Histologically confirmed prostatic adenocarcinoma with localised or metastatic disease
• Karnofsky index score of 70% or more
• Started on androgen deprivation therapy (both medical or surgical), for at least 3 months at baseline
• Baseline daily hot flush score ≥4

Exclusion criteria

• Patients treated with drugs related to the study medications or with potential effect for vasomotor symptoms, including selective serotonin-re-uptake inhibitors, steroid hormones, clonidine, gabapentin, veralipride, or β-alanine
• Concomitant use of CYP1A2 inhibitors, e.g. fluoroquinolone, fluovoxamine, cimetidine, propranolol, verapamil, acyclovir, allopurinol, theophylline, etc.
• Active liver disease including:

\- cirrhosis - liver failure - jaundice - elevated total or direct bilirubin - abnormal ALT / AST - abnormal INR

• Severe (eGFR 15 to less than 30 mL/min/1.73 m2) renal impairment or end-stage renal disease (eGFR less than 15 mL/min/1.73 m2)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Hong Kong · 1 center

• Prince of Wales Hospital — Shatin

Publications

• Challapalli A, Edwards SM, Abel P, Mangar SA. Evaluating the prevalence and predictive factors of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single institution experience. Clin Transl Radiat Oncol. 2018 Mar 21;10:29-35. doi: 10.1016/j.ctro.2018.03.002. eCollection 2018 Mar. PMID 29928703
• Teleni L, Chan RJ, Chan A, Isenring EA, Vela I, Inder WJ, McCarthy AL. Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials. Endocr Relat Cancer. 2016 Feb;23(2):101-12. doi: 10.1530/ERC-15-0456. Epub 2015 Nov 19. PMID 26584972
• Irani J, Salomon L, Oba R, Bouchard P, Mottet N. Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial. Lancet Oncol. 2010 Feb;11(2):147-54. doi: 10.1016/S1470-2045(09)70338-9. Epub 2009 Dec 4. PMID 19963436
• Moraska AR, Atherton PJ, Szydlo DW, Barton DL, Stella PJ, Rowland KM Jr, Schaefer PL, Krook J, Bearden JD, Loprinzi CL. Gabapentin for the management of hot flashes in prostate cancer survivors: a longitudinal continuation Study-NCCTG Trial N00CB. J Support Oncol. 2010 May-Jun;8(3):128-32. PMID 20552926
• Frisk J, Spetz AC, Hjertberg H, Petersson B, Hammar M. Two modes of acupuncture as a treatment for hot flushes in men with prostate cancer--a prospective multicenter study with long-term follow-up. Eur Urol. 2009 Jan;55(1):156-63. doi: 10.1016/j.eururo.2008.02.002. Epub 2008 Feb 14. PMID 18294761
• 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
• Morga A, Ajmera M, Gao E, Patterson-Lomba O, Zhao A, Mancuso S, Siddiqui E, Kagan R. Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause. Menopause. 2024 Jan 1;31(1):68-76. doi: 10.1097/GME.0000000000002281. Epub 2023 Nov 27. PMID 38016166

Identifiers

NCT: NCT07568236 · CRE-2025.427-T

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗