Clinical Trials /

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

NCT04339751

Description:

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.

Related Conditions:
  • ACTH-Producing Pituitary Gland Adenoma
  • Cushing Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
  • Official Title: The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease

Clinical Trial IDs

  • ORG STUDY ID: 200019
  • SECONDARY ID: 20-N-0019
  • NCT ID: NCT04339751

Conditions

  • Cushing's Disease

Interventions

DrugSynonymsArms
Vorinostatsingle center, prospective pilot study

Purpose

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

      Objective

      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.

      Study Population

      Adult (> 18 years old) patients with a diagnosis of Cushing s disease that qualify for
      surgery through a different NIH protocol (#03-N-0164).

      Design

      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.

      Outcome Measures

      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.-
    

Trial Arms

NameTypeDescriptionInterventions
single center, prospective pilot studyExperimentaleffectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease
  • Vorinostat

Eligibility Criteria

        -  INCLUSION CRITERIA:

        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.

        EXCLUSION CRITERIA:

          -  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.

          -  Pregnancy or lactation.

          -  Presence of any disease that will obscure toxicity or dangerously alter drug
             metabolism (such as uncontrolled diabetes or bleeding disorders)

          -  Currently receiving other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to vorinostat, such as valproate.

          -  Currently taking another HDACi, such as valproate.

          -  Currently taking coumadin or its derivative anticoagulants.

          -  Currently taking any other medication to reduce cortisol or ACTH levels
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Midnight Plasma ACTH
Time Frame:Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Safety Issue:
Description: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

Measure:Urinary Free Cortisol
Time Frame:Day -1, Day 0-1, Day 2, Day 4-6, Discharge
Safety Issue:
Description:Relative change in 24-hour urinary free cortisol during 7 day administration of Vorinostat

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Institute of Neurological Disorders and Stroke (NINDS)

Trial Keywords

  • SAHA
  • CD

Last Updated

April 16, 2020