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

NCT04339751 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 20001920-N-0019
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cushing's Disease

Keywords

SAHA; CD

Outcome Measures

Primary Outcomes (1)

• Midnight Plasma ACTH

  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).

  Day -1, Day 0-1, Day 2, Day 4-6, Discharge

Secondary Outcomes (1)

• Urinary Free Cortisol

  Day -1, Day 0-1, Day 2, Day 4-6, Discharge

Study Arms (1)

single center, prospective pilot study

EXPERIMENTAL

effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease

Drug: Vorinostat

Interventions

Vorinostat DRUG

Administration of Vorinostat

single center, prospective pilot study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Adult patients (18 years and older)
• Confirmed biochemical diagnosis of Cushing s disease (primary or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH.
• Surgical candidate for resection of ACTH producing pituitary adenoma
• Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.
• Able to provide written informed consent at the time of study enrollment.
• Participants who are physically able to become pregnant must use an effective form of birth control from 14 days prior to enrollment through 6 months following the last dose of vorinostat. Participants who are able to father a child must use an effective form of birth control from Day 0 through 3 months following the last dose of vorinostat.

You may not qualify if:

• Patients who have been previously treated with vorinostat.
• Patients who have received sellar radiation.
• Significant medical illnesses that in the investigator s opinion cannot be adequately controlled or would compromise the patient s ability to tolerate this vorinostat.
• Any history of cancer, unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
• History of thromboembolic disorder or deep vein thrombosis
• Presence of abnormal hematological and biochemical parameters, (such as anemia or thrombocytopenia) as defined as:
• Neutrophil count \< 1.5 K//micro L
• Hemoglobin \< 8.0 g/dL.
• Hematocrit \< 0.75x LLN (lower limit of normal)
• RBC count \< 0.75x LLN
• Platelet count \< 100 x 10\^3 cells/micro L.
• Prothrombin time-international normalized ratio (PT-INR) \> 1.5x ULN or Activated partial thromboplastin time (aPTT) \> 1.5x ULN, with the exception of patients on prophylactic anticoagulation therapy
• Serum bilirubin level \> 1.5x ULN.
• Active infection being currently treated with systemic antibiotics.
• Serious concurrent medical illness including renal failure (creatinine \>3.0x - 6.0x ULN) liver failure (ALT/AST \>5.0x - 20.0x ULN) or severe cardio-respiratory disease.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003 Dec;88(12):5593-602. doi: 10.1210/jc.2003-030871.

  PMID: 14671138 BACKGROUND

• Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res. 1994 Sep;2(5):486-508. doi: 10.1002/j.1550-8528.1994.tb00097.x. No abstract available.

  PMID: 16353601 BACKGROUND

• Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-17. doi: 10.1016/S0140-6736(06)68699-6.

  PMID: 16698415 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Prashant Chittiboina, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 9, 2020
• Study Start: April 11, 2025
• Primary Completion: April 11, 2025
• Study Completion: April 11, 2025
• Last Updated: April 15, 2025

Record last verified: 2025-04

Locations

US (1)