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
- Conditions
- Prostate CancerProstate Cancer Metastatic DiseaseProstate CarcinomaVasomotor DisturbanceProstate Cancer (Adenocarcinoma)Prostate Cancer RecurrentProstate NeoplasmProstate AdenocarcinomaProstate Cancer With Bone MetastasisVasomotor Symptoms; Hot Flashes
- Interventions
- Drug: Placebo
- Registration Number
- NCT06957691
- Lead Sponsor
- Shehzad Basaria, M.D.
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 60
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fezolinetant fezolinetant - reference formulation Daily oral administration at a dose of 45 mg Placebo Placebo Daily oral administration
- Primary Outcome Measures
Name Time Method Change in the Frequency of Vasomotor Symptoms Through Daily Hot Flash Diary from Baseline to 12 Weeks From baseline to the end of treatment at 12 weeks. Participants achieved a response if they had a significant decrease in scores in the hot flash diary.
Hepatic safety, as assessed by measuring liver function tests From baseline to the end of treatment at 12 weeks. Fezolinetant was considered safe if liver function tests did not change significantly.
- Secondary Outcome Measures
Name Time Method Change in overall quality of life, as assessed using the Short Form-36 questionnaire From baseline to the end of treatment at 12 weeks. The Short Form-36 scores range from 0 to 100, with higher scores meaning a better outcome. Participants improved if they had a significant increase in their Short Form-36 scores.
Change in sexual function, as assessed using the Sexual Arousal, Interest and Drive questionnaire From baseline to the end of treatment at 12 weeks. The Sexual Arousal, Interest and Drive questionnaire scores range from 0 to 100, with higher scores meaning better outcome. Participants improved if they had a significant increase in Sexual Arousal, Interest and Drive scores.
Change in fatigue, as assessed using the using the Hypogonadism Energy Diary questionnaire From baseline to the end of treatment at 12 weeks. The Hypogonadism Energy Diary scores range from 0 to 100, with higher scores meaning better outcome. Participants improved if they had a significant increase in Hypogonadism Energy Diary scores.
Change in fatigue, as assessed using the using the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire From baseline to the end of treatment at 12 weeks. The Functional Assessment of Chronic Illness Therapy - Fatigue scores range from 0 to 160, with higher scores meaning better outcome. Participants improved if they had a significant increase in Functional Assessment of Chronic Illness Therapy - Fatigue scores.
Change in fasting glucose level From baseline to the end of treatment at 12 weeks. Participants improved if they had a significant decrease in fasting glucose level.
Change in glycated hemoglobin (HbA1c) level From baseline to the end of treatment at 12 weeks. Participants improved if they had a significant decrease in glycated hemoglobin (HbA1c) level.
Change in fasting lipid levels From baseline to the end of treatment at 12 weeks. Participants improved if they had a significant decrease in fasting lipid levels.
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 12 weeks. The Hot Flash-Related Daily Interference Scale scores range from 0 to 10, with higher scores meaning a worse outcome. Participants improved if they had a significant decrease in their Hot Flash-Related Daily Interference Scale scores.
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 12 weeks. The Patient-Reported Outcomes Measurement Information System Sleep Disturbance scores range from about 30 to 80, with lower scores meaning better outcome. Patients improved if they had a significant decrease in Patient-Reported Outcomes Measurement Information System Sleep Disturbance scores.
Change in mood, as assessed using the Positive and Negative Affect Schedule questionnaire From baseline to the end of treatment at 12 weeks. The Positive and Negative Affect Schedule questionnaire measures two dimensions of mood, Positive Affect and Negative Affect. The scores in each dimension range from 10 to 50. A higher score in the Positive Affect dimension means a better outcome, and a higher score in the Negative Affect dimension means a worse outcome. Participants improved if they had a significant increase in the Positive Affect dimension scores and a significant decrease in the Negative Affect dimension scores in the Positive and Negative Affect Schedule questionnaire.
Change in inflammatory status, as assessed by measuring high-sensitivity C-reactive protein (hsCRP) levels From baseline to the end of treatment at 12 weeks. Participants improved if they had a significant decrease in high-sensitivity C-reactive protein (hsCRP) levels.