Prostate Adenocarcinoma
Conditions
Brief summary
To evaluate the effect of Osanetant on testosterone levels in men with prostate cancer within 28 days of therapy.
Detailed description
Primary: To evaluate the effect of Osanetant on testosterone levels in men with prostate cancer within 28 days of therapy. Secondary: * To evaluate the effect Osanetant on pituitary hormones (LH/FSH) and estrogen within 28 days of therapy. * To evaluate the effect of Osanetant on PSA levels after 28 days (approximately 4 weeks) of therapy.
Interventions
DRUGOsanetant
To evaluate the effect of Osanetant on the testosterone levels.
Sponsors
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, pilot clinical trial
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 adenocarcinoma of the prostate (PCa) * Planned radical prostatectomy within the study period * Testosterone \>150ng/ml * Adequate organ function, defined as follows: Result Date * Leukocytes \>1.5K/UL * Absolute Neutrophil Count \>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 * Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN * Men with partners of child-bearing 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. Men of child-bearing potential must not father a child or donate sperm while receiving investigational treatment. Following treatment (standard of care prostatectomy) there is no further child-bearing potential.
Exclusion criteria
* Current or recent (within 6 months) use of testosterone/estrogen modulating agents (leuprolide, degarelix, bicalutamide, enzalutamide, apalutamide, darolutamide, abiraterone, systemic ketoconazole, tamoxifen, etc) * Current use of CYP3A4 inhibitors * Subjects 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. * Cognitive impairment (defined as the presence of diagnosed dementia) * Impaired renal function: Cr \>1.8 * Medical history of osteoporosis * Current systemic corticosteroid, long-term opioid, spironolactone, or eplerenone use * 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. * Active COVID-19 infection * Any history of underlying liver disorder, including hepatitis (see below) * Any evidence of acute or chronic hepatitis B or C on screening testing * Elevation of any or all liver enzymes (ALT, 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 ECG abnormalities at baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of Osanetant on the testosterone levels. | 28 days | We will test the ability of Osanetant to suppress testosterone production. A single arm pilot study of Osanetant at 200mg twice daily will be performed. Testosterone levels at baseline will be compared to levels at day 2, 3, 7 ,14, and 28 days of therapy. The overall effect of Osanetant on testosterone levels and the proportion of men achieving castrate levels of testosterone (\<50ng/ml) will be assessed. Additionally, the reversibility of this effect will be assessed by evaluating the testosterone levels at 6-8 weeks posttreatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of Osanetant on LH levels. | 28 days | Levels of luteinizing hormone (LH) will be measured at baseline and days 2, 3, 7 ,14, and 28. These will be compared at each time point in order to assess the impact of NK3RA on these hormonal parameters. |
| To evaluate the effect of Osanetant on FSH levels. | 28 days | Levels of follicle stimulating hormone (FSH) will be measured at baseline and days 2, 3, 7 ,14, and 28. These will be compared at each time point in order to assess the impact of NK3RA on these hormonal parameters. |
| To evaluate the effect of Osanetant on estradiol levels | 28 days | Levels of estradiol will be measured at baseline and days 2, 3, 7 ,14, and 28. These will be compared at each time point in order to assess the impact of NK3RA on these hormonal parameters. |
| To evaluate the effect of Osanetant on PSA levels. | 28 days | PSA will be compared at baseline and 28 days of therapy in order to evaluate the end biochemical efficacy of Osanetant on men with prostate cancer undergoing curative intent therapy. |
Countries
United States
Outcome results
None listed