Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease

Cushing's Disease Clinical Trial

Official title: The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing's Disease

Status Recruiting

Clinical Trial Summary

Background:

Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. It can lead to decreased quality of life and early death. The current best treatment for Cushing s disease is surgery. If surgery does not work or if the tumor returns, there are no more good treatment options. Vorinostat, which is approved to treat a type of lymphoma, might be a treatment option.

Objective:

To test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.

Eligibility:

People ages 18 and older who have Cushing s disease and are scheduled for surgery under protocol 03-N-0164 to remove a tumor in their pituitary gland

Design:

Participants will be screened under protocol 03-N-0164.

Participants will stay in the hospital for 8 days before their surgery.

On the first day, participants will have a physical exam and blood tests. They will have their urine collected for testing all day. They will have an ECG: For this, small metal disks or sticky electrode pads will be placed on their chest to record heart activity.

For the next 7 days, participants will have blood tests and all-day urine collection. They will drink at least 2 liters of fluid per day. They will take the study drug by mouth each morning.

On the eighth day, participants will have their surgery. Leftover tissue will be collected for research.

On the day they are discharged from the hospital, participants will have a physical exam and blood tests.

Clinical Trial Description

Study Description

This is a single center, prospective pilot study of effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease. Surgery for resection of ACTH producing pituitary adenoma will be offered at the NIH under another protocol (03-N-0164) as part of standard clinical care. Eligible subjects will be admitted to the Clinical Center for one week prior to surgery, during which time oral vorinostat will be administered daily.

Objectives

Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. The resulting increase in cortisol levels caused by increased ACTH causes a severe condition that leads to decreased quality of life and early death. The current best first treatment for Cushing s disease is surgery. However, if surgery is unsuccessful or if the tumor returns, there are no good treatment options for patients. In laboratory studies, we discovered that a previously FDA approved oral medication Vorinostat was able to kill tumors cells and reduce ACTH secretion. We want to test whether this drug can be used in patients with Cushing s disease to reduce ACTH levels.

Primary Objective: to determine whether vorinostat reduces midnight plasma ACTH level

Secondary Objectives: to evaluate the effect of vorinostat on urine cortisol levels

Endpoints

Primary Endpoint: midnight plasma ACTH level on the last day of drug administration. Secondary Endpoints: serum cortisol change during drug administration. ;

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Adenoma
• Cushing's Disease
• Pituitary ACTH Hypersecretion
• Pituitary Neoplasms

• NCT number: NCT04339751
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Michaela X Cortes
• Phone: (301) 496-2921
• Email: michaela.cortes@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: June 26, 2024
• Completion date: December 1, 2024