Osanetant for Reducing the Severity of Hot Flashes in Men Receiving Androgen Deprivation Therapy for Prostate Adenocarcinoma, The POSH-MAP Trial

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 or antagonist 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) (HFS: total number of hot flashes for 1 week multiplied by the average severity/week) >= 100
• Leukocytes >= 1.5 k/ul
• Absolute neutrophil count (ANC) >= 1.5 k/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 >= 100 k/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
• 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 contraception 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 cT1 renal cell carcinoma on active surveillance, or the following malignancies treated with curative intent via surgical resection: 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 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [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, human immunodeficiency virus (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
• Participants who take narrow therapeutic index pharmacologic agents that are highly human protein-bound, including warfarin, digoxin, amiodarone, and phenytoin
• Any history of underlying liver disorder, including hepatitis
• Any evidence of acute or chronic hepatitis B or C on screening testing
• Elevation of any or all liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin) above the upper limit of normal (ULN) at baseline testing prior to enrollment
• A family history of hepatitis or currently living with a person who has been given a diagnosis of hepatitis
• A history of or currently working as a sex worker
• A history of or currently using intravenous (IV) drugs
• A self-reported history of alcoholic dependency or abuse
• A history of or current diagnosis of cardiovascular disease including heart failure, coronary artery disease, uncontrolled hypertension, uncontrolled diabetes; arrhythmias (or history of), or clinically relevant electrocardiogram (ECG) abnormalities at baseline