Clinical trial NCT06957691: 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
Official title: 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 Trial)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Prostate Cancer (Adenocarcinoma)
Prostate Cancer Metastatic Disease
Prostate Cancer Recurrent
Prostate Carcinoma
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
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2025-05-04
Enrollment: 60
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the Frequency of Vasomotor Symptoms Through Daily Hot Flash Diary from Baseline to 12 Weeks
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Hepatic safety, as assessed by measuring liver function tests
timeFrame: From baseline to the end of treatment at 12 weeks.
Secondary outcomes:
measure: Change in quality-of-life symptoms related to hot flashes, as assessed using the Hot Flash-Related Daily Interference Scale
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in overall quality of life, as assessed using the Short Form-36 questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in sleep quality, as assessed using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in mood, as assessed using the Positive and Negative Affect Schedule questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in sexual function, as assessed using the Sexual Arousal, Interest and Drive questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in inflammatory status, as assessed by measuring high-sensitivity C-reactive protein (hsCRP) levels
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in fatigue, as assessed using the using the Hypogonadism Energy Diary questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in fatigue, as assessed using the using the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in fasting glucose level
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in glycated hemoglobin (HbA1c) level
timeFrame: From baseline to the end of treatment at 12 weeks.
measure: Change in fasting lipid levels
timeFrame: From baseline to the end of treatment at 12 weeks.
Other outcomes:
Locations:
Study officials:
affiliation: Brigham and Women's Hospital
name: Shehzad S Basaria, MD
role: PRINCIPAL_INVESTIGATOR
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