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 (Fezo-ADT)

Shehzad Basaria, M.D.

Status and phase: Begins enrollment in 2 months; Phase 2

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

Treatments: Drug: fezolinetant - reference formulation; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06957691

GR1000264

Details and patient eligibility

About

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 and 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 12 weeks
• Visit the clinic once every 4 weeks for checkups and tests
• Keep a diary of the number of times and intensity that they experience hot flashes

Full description

Prostate cancer is the most common type of cancer in men. At the time of initial diagnosis, most men have disease that is confined to the prostate and are typically managed through surveillance or local treatments, such as prostatectomy or radiation therapy. Since the prostate relies on androgens (male hormones), androgen deprivation therapy is the primary treatment for patients with locally advanced, recurrent, or metastatic prostate cancer.

Androgen deprivation therapy involves suppressing the production of androgens in men, which can be achieved through orchiectomy (removal of the testes) or medications like gonadotropin-releasing hormone agonists or antagonists that lower serum testosterone levels to a castrate range (less than 20 ng/dL). In men, 95% of serum estrogen comes from the aromatization of testosterone. Consequently, androgen deprivation not only leads to androgen deficiency but also results in near-absolute estrogen deficiency. The absence of sex hormones in these patients can cause numerous adverse effects, including sexual dysfunction, and loss of muscle and bone. Among these side effects, vasomotor symptoms (such as hot flashes) are particularly debilitating. These symptoms are characterized by sudden feelings of intense heat that spread throughout the body, prompting the activation of heat-dissipation mechanisms to lower body temperature.

Hot flashes are reported by 70-80% of men undergoing androgen deprivation therapy, typically beginning a few weeks after treatment starts, with most men experiencing more than five episodes daily. These vasomotor symptoms significantly affect the patient's quality of life, sleep quality, concentration, and overall productivity. Despite the burden they impose, effective treatments for hot flashes in men undergoing androgen deprivation therapy are still lacking.

The introduction of neurokinin 3 (NK3) receptor antagonists has brought hope to this area. Fezolinetant is a selective NK3 receptor antagonist that has recently been approved for treating moderate to severe vasomotor symptoms in menopausal women. Given that the underlying cause of vasomotor symptoms in both menopausal women and men on androgen deprivation therapy stems from estrogen deficiency, fezolinetant offers an opportunity to assess its efficacy and safety for male patients.

No previous studies have evaluated the effectiveness of NK3 receptor antagonists on vasomotor symptoms in men undergoing androgen deprivation therapy for prostate cancer. Since prostate cancer is the most prevalent solid tumor in men and vasomotor symptoms are common, distressing, and highly burdensome, a trial demonstrating the safety and efficacy of fezolinetant could provide clinicians and patients with a novel, effective, safe, and easy-to-administer treatment that has the potential to transform care for these patients.

Enrollment: 60 estimated patients

Sex: Male

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male sex
• Age 40 years and older
• Diagnosis of prostate cancer
• Androgen deprivation therapy
• Presence of 5 or more hot flashes a day that are considered moderate to severe
• Ability to sign the inform consent

Exclusion criteria

• Use of abiraterone acetate
• Use of docetaxel and other chemotherapeutic agents
• Liver cirrhosis
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal
• Total bilirubin ≥ 2 times 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 agents or herbal compounds
• Use of CYP1A2 inhibitors

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Fezolinetant

Experimental group

Description:

Daily oral administration at a dose of 45 mg

Treatment:

Drug: fezolinetant - reference formulation

Placebo

Placebo Comparator group

Description:

Daily oral administration

Treatment:

Drug: Placebo