Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
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|ClinicalTrials.gov Identifier: NCT04339751|
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : November 26, 2020
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.
To test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.
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
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.
|Condition or disease||Intervention/treatment||Phase|
|Cushing's Disease||Drug: Vorinostat||Phase 2|
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.
Adult (> 18 years old) patients with a diagnosis of Cushing s disease that qualify for surgery through a different NIH protocol (#03-N-0164).
We will recruit patients with Cushing s disease who have surgery planned for removal of the pituitary tumor. If they consent, we will admit them as inpatients for 8 days before surgery. After a thorough laboratory investigation, we will administer Vorinostat by mouth daily for 7 days. During this time, we will measure the levels of ACTH and glucocorticoid hormones in the blood and urine daily. On the 8th day, we will perform the surgery as planned. We also will test tissue obtained during surgery to evaluate the drug s effect on the tumors.
The main outcome measure is the midnight plasma ACTH level on the last day of drug administration. A secondary outcome measure is the serum cortisol change during drug administration.-
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease|
|Estimated Study Start Date :||December 1, 2020|
|Estimated Primary Completion Date :||June 15, 2021|
|Estimated Study Completion Date :||June 15, 2021|
Experimental: single center, prospective pilot study
effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease
Administration of Vorinostat
- Midnight Plasma ACTH [ Time Frame: 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).
- Urinary Free Cortisol [ Time Frame: 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04339751
|Contact: Gretchen C Scott, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Prashant Chittiboina, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|