Pilot of Osanetant to Reduce Severity of Hot Flashes in Men With Adenocarcinoma of the Prostate

Study Overview
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Brief Summary
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To evaluate the preliminary efficacy of in reducing the frequency and severity of hot flashes in men on androgen deprivation therapy (ADT).

Official Title
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Pilot of Osanetant to Reduce Severity of Hot Flashes in Men With Adenocarcinoma of the Prostate (POSH-MAP)

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Osanetant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent Males ≥ 18 years Histologic diagnosis of prostate cancer (PCa) Undergoing active treatment with ADT within ≥ 30 days prior to randomization Using either an gonadotropin releasing hormone (GNRH) agonist with a planned duration covering the 8 weeks of the study or are status post bilateral orchiectomy, Have a castrate level of testosterone (≤ 50 ng/dL) at enrollment Have moderate-to-severe hot flashes defined as Seven (7) or more hot flashes per day Total hot flash severity (HFS: total number of hot flashes for 1 week multiplied by the average severity/week) ≥ 100 Adequate organ function, defined as follows: Result Date Leukocytes > 1.5K/UL Absolute Neutrophil Count (ANC) >1.5K/UL NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the patient. Platelets >100K/UL Hemoglobin ≥ 9 g/dL Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN Aspartate aminotransferase and alanine aminotransferase ≤ 1.5 x ULN Women of child-bearing potential and men with partners of childbearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 30 days following completion of therapy. Exclusion Criteria: Concurrent invasive malignancy or invasive malignancy within 2 years except for chronic lymphocytic leukemia/small lymphocytic lymphoma on surveillance, suspected or proven clinical stage 1 (cT1) renal cell carcinoma on active surveillance, or the following malignancies treated with curative intent via surgical resection: carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, low-grade non-muscle-invasive urothelial carcinoma, non-melanoma skin cancer. Simultaneously enrolled in any therapeutic clinical trial Current or anticipating use of other pharmacologic anti-neoplastic (including hormonal), or investigational agents while participating in this study. Concurrent treatment with radiotherapy is permitted. Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements Has a known allergic reaction to any excipient contained in the study drug formulation Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment. Participants using the following medications within 2 weeks prior to first dosing (or within 5 times the half-life of that medication, whichever is longer) will be excluded from the study: Inhibitors of CYP3A4 (including but not limited to macrolide antibiotics, HIV protease inhibitor, azole antifungal drugs, cyclosporine, calcium channel inhibitor, cimetidine) Inducers of CYP3A4 (including but not limited to rifampicin, carbamazepine, efavirenz, bosentan, modafinil, St. John's Wort), Medications with narrow therapeutic index that are metabolized CYP3A4 and/or CYP2D6 are not allowed from screening until up to 5 half-lives after last dose of Osanetant is administered.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single-arm pilot
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pilot Trial: Osanetant 28 Days<br>Osanetant 200 mg orally, twice per day for 28 days. | Drug: Osanetant<br>* Osanetant 200 mg orally, twice per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the preliminary efficacy of in reducing the frequency and severity of vasomotor symptoms (VMS) in men on androgen deprivation therapy (ADT). | Efficacy will be assessed using a composite outcome of median weekly hot flash frequency and severity at week 4 compared to baseline. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of Osanetant on follicle stimulating hormone for men with prostate cancer on ADT. | Levels of follicle stimulating hormone (FSH) will be measured at week 4 will be compared to baseline. | 28 days | 
| To evaluate the effect of Osanetant on luteinizing hormone for men with prostate cancer on ADT. | luteinizing hormone (LH) will be measured at week 4 will be compared to baseline. | 28 days | 
| To evaluate the effect of Osanetant on testosterone for men with prostate cancer on ADT. | testosterone will be measured at week 4 will be compared to baseline. | 28 days | 
| To evaluate the effect of Osanetant on estradiol for men with prostate cancer on ADT. | estradiol will be measured at week 4 will be compared to baseline. with prostate cancer on ADT | 28 days | 
| Functional Assessment of Cancer Therapy-Prostate (FACT-P) | To evaluate the impact of Osanetant on global quality of life with Functional Assessment of Cancer Therapy-Prostate (FACT-P) | 28 days | 
| EuroQOL 5-dimension | To evaluate the impact of Osanetant on global quality of life with a visual analog scale from EuroQOL 5-dimension, 5-level (EQ-5D-5L). The EQ-5D-5L visual analog scale is 0-100 with higher numbers being better. | 28 days | 
| Patient Health Questionnaire-9 question (PHQ-9). | To evaluate the impact of Osanetant on depressive symptoms on Patient Health Questionnaire-9 question (PHQ-9). | 28 days | 
| General Anxiety Disorder-7 question (GAD-7) | To evaluate the impact of Osanetant on anxiety symptoms on General Anxiety Disorder-7 question (GAD-7). | 28 days | 
| Hot Flash Related Daily Interference Scale (HFRDIS). | To evaluate the impact of Osanetant on hot flash interference using the Hot Flash Related Daily Interference Scale (HFRDIS). The hot flash daily interference scale has a minimum of 0 and a max of 100, with higher scores indicating more interference (which is worse). | 28 days |