Clinical trial NCT05607342: Pilot of Osanetant to Reduce Testosterone in Men With Adenocarcinoma of the Prostate
Official title: Pilot of Osanetant to Reduce Testosterone in Men With Adenocarcinoma of the Prostate (PORT-MAP)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Prostate Adenocarcinoma
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2022-11-07
Enrollment: 1
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, pilot clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the effect of Osanetant on the testosterone levels.
timeFrame: 28 days
Secondary outcomes:
measure: To evaluate the effect of Osanetant on LH levels.
timeFrame: 28 days
measure: To evaluate the effect of Osanetant on FSH levels.
timeFrame: 28 days
measure: To evaluate the effect of Osanetant on estradiol levels
timeFrame: 28 days
measure: To evaluate the effect of Osanetant on PSA levels.
timeFrame: 28 days
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, Westwood Campus
state: Kansas
Study officials:
References: