Fimepinostat treatment for Cushing Disease

Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease

This study is testing a new drug called Fimepinostat to see if it can safely help people with Cushing Disease feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, Los Angeles (Academic / other)
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT05971758 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of Fimepinostat, a combination HDAC and PI3-kinase inhibitor, in treating patients with Cushing Disease. It is a pilot, short-term phase II study conducted at the University of California, Los Angeles, with a 2-arm design examining two different doses of the drug. The trial aims to recruit patients with de novo, persistent, or recurrent Cushing Disease and will last for 4 weeks. The results will help determine the appropriate dosing for larger future studies.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed pituitary origin Cushing syndrome.

Not a fit: Patients with Cushing Disease not meeting the inclusion criteria or those who have not completed the required washout periods for prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from Cushing Disease.

How similar studies have performed: While this approach is based on pre-clinical data, the specific use of Fimepinostat for Cushing Disease is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Male and female patients at least 18 years old
* Patients with confirmed pituitary origin Cushing syndrome defined as 1, 2\& 3 or 4 \& 5 below:

  1. Persistent hypercortisolism defined as a mean of 3 consecutive 24h UFC at baseline assessment ≥ 1.3x ULN
  2. Normal or elevated plasma ACTH levels
  3. Pituitary adenoma \> 4mm visible on MRI or inferior petrosal sinus sampling (IPSS) central to peripheral ACTH gradient \>2 at baseline and/or \>2 after DDAVP stimulation.
  4. Recurrent or persistent CD defined as pathologically confirmed previously resected pituitary ACTH-secreting tumor, and 24 hour UFC \>ULN at least 4 weeks after pituitary surgery.
  5. Patients on medical treatment for CD. Washout periods will be completed as below before screening: Inhibitors of steroidogenesis (metyrapone, ketoconazole, osilodristat,

     * Levo-ketoconazole): 2 weeks
     * SRLs (pasireotide): 2 weeks
     * Progesterone receptor antagonist (mifepristone): 2 weeks
     * Dopamine agonists (cabergoline): 4 weeks
     * CYP3A4 strong inducers or inhibitors: varies between drugs; minimum 5-6 times the half-life of drug

Exclusion Criteria:

* Patients with compromised visual fields, or evidence of visual changes within past 6 months
* Patients with sellar tumor abutting or compressing the optic chiasm on MRI and normal visual fields
* Patients with Cushing's syndrome not due to an ACTH-secreting pituitary tumor
* Patients who have undergone major surgery including pituitary surgery within 1 month of screening or who have any major surgical procedures planned across the study period
* Patients with serum potassium \< 3.5 mEq/L unless stably controlled on potassium supplementation
* Patients with poorly-controlled Diabetes mellitus evidenced by HbA1c levels \>8
* Patients with poorly controlled hypertension (i.e. blood pressure ≥ 160/100 mm Hg)
* Patients who have clinically significant cardiovascular impairment, as evidenced by the presence of bradycardia, ventricular tachycardia, history of myocardial infarction within past year, or any other cardiovascular impairment that may pose significant health risk in view of the investigator.
* Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST \>1.5 x ULN, serum total bilirubin \>ULN, serum albumin \<0.67 x LLN at screening
* Patients with renal disease or history of renal disease with creatinine clearance of 30 cm3/min or less and/or creatinine \> 1.5 mg/dl at screening
* Patients not biochemically euthyroid. Patients receiving thyroid-replacement therapy must be on a stable dose for at least 3 months.
* Patients who are known to be positive for HIV, or any other condition that significantly compromises subject's immune system.
* History of alcohol abuse or illicit substance use within past year.
* Female patients who are pregnant or lactating or are of childbearing potential unless willing to practice acceptable method of birth control. Women participating in the trial must employ double barrier method through oral contraceptive or diaphragm with partner utilizing a condom. Abstinence is an acceptable form of birth control if routinely practiced. Male participants must utilize a condom with spermicidal cap/jelly and agree to not donate sperm for up to 3 months beyond main study period.
* Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to screening or within 5 half-lives of the investigational treatment whichever is longer.
* Patients with concomitant treatment of strong CYP3A4 inducers or inhibitors.
* Patients who have received pituitary irradiation within the last 5 years prior to the baseline visit
* Patients with known hepatitis B surface antigen (HbsAg) positivity
* Patients with known hepatitis C antibody (anti-HCV) positivity

Where this trial is running

Los Angeles, California

• Ronald Reagan Medical Center — Los Angeles, California, United States (Recruiting)

Study contacts

• Study coordinator: Anthony Heaney, MD

Conditions Cushing Disease