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

This is an interventional treatment trial for Cushing's Disease focused on measuring SAHA, CD Read More

• 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