Fezolinetant for the Improvement of Hot Flashes in Men with Prostate Cancer Undergoing Androgen Deprivation Therapy, Fezo-ADT Trial

Inclusion Criteria

• Male sex
• Age 40 years and older
• Diagnosis of PCa
• ADT with gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists and plan to continue to receive it for at least 24 weeks. Concomitant use of androgen receptor antagonists (e.g., bicalutamide, enzalutamide, apalutamide, darolutamide) is permitted, as the incidence of hepatotoxicity is low with these compounds. Participants who have received at least 4 weeks of ADT will be enrolled, as vasomotor symptoms are evident around this time
• Presence of ≥ 5 moderate-to-severe hot flashes per day or ≥ 35 moderate-to-severe hot flashes over 7 days, based on Food and Drug Administration (FDA) definition of severity
• Ability to sign the informed consent

Exclusion Criteria

• Use of abiraterone acetate, due to its increased risk of hepatotoxicity. Thus, this drug should be avoided in this proof-of-concept study assessing the safety of fezolinetant
• Use of docetaxel and other chemotherapeutic agents, due to their increased risk of severe adverse events, such as bone marrow depression and opportunistic infections. Thus, patients receiving concomitant chemotherapy will be excluded from this proof-of-concept study assessing the safety of fezolinetant
• Liver cirrhosis
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ the upper limit of normal (ULN) for the evaluating lab
• Total bilirubin ≥ the ULN for the evaluating lab
• Renal impairment, as determined by an estimated glomerular filtration rate < 30 mL/min
• Use of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, sedatives, or hypnotics, as some of these drugs are currently used in the treatment of hot flashes
• Use of over-the-counter agents or herbal compounds, as these compounds may influence hot flashes
• Current use of CYP1A2 inhibitors, including, but not limited to, fluvoxamine, mexiletine, cimetidine, fluoroquinolones, isoniazid, verapamil, and licorice
• Use of alcohol within 2 weeks prior to the baseline visit
• Inability to abstain from alcohol use during the intervention period