Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
- Registration Number
- NCT04339751
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 22
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description single center, prospective pilot study Vorinostat effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease
- Primary Outcome Measures
Name Time Method Midnight Plasma ACTH Day -1, Day 0-1, Day 2, Day 4-6, Discharge Relative change in midnight plasma ACTH. Dichotomized relative change using 20% as a cutoff (which is considered as clinical important): relative change \>20% for reduction and relative change \<=20% for no change).
- Secondary Outcome Measures
Name Time Method Urinary Free Cortisol Day -1, Day 0-1, Day 2, Day 4-6, Discharge Relative change in 24-hour urinary free cortisol during 7 day administration of Vorinostat
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States