Ignite Creation Date:
2025-12-24 @ 11:43 PM
Ignite Modification Date:
2025-12-31 @ 4:19 PM
Study NCT ID:
NCT04339751
Status:
WITHDRAWN
Last Update Posted:
2025-04-15
First Post:
2020-04-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D047748', 'term': 'Pituitary ACTH Hypersecretion'}], 'ancestors': [{'id': 'D006964', 'term': 'Hyperpituitarism'}, {'id': 'D010900', 'term': 'Pituitary Diseases'}, {'id': 'D007027', 'term': 'Hypothalamic Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077337', 'term': 'Vorinostat'}], 'ancestors': [{'id': 'D000813', 'term': 'Anilides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D006877', 'term': 'Hydroxamic Acids'}, {'id': 'D006898', 'term': 'Hydroxylamines'}, {'id': 'D006880', 'term': 'Hydroxy Acids'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Lack of enrollment.', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2025-04-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2025-04-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-11', 'studyFirstSubmitDate': '2020-04-08', 'studyFirstSubmitQcDate': '2020-04-08', 'lastUpdatePostDateStruct': {'date': '2025-04-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-04-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-04-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Midnight Plasma ACTH', 'timeFrame': 'Day -1, Day 0-1, Day 2, Day 4-6, Discharge', '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).'}], 'secondaryOutcomes': [{'measure': 'Urinary Free Cortisol', 'timeFrame': 'Day -1, Day 0-1, Day 2, Day 4-6, Discharge', 'description': 'Relative change in 24-hour urinary free cortisol during 7 day administration of Vorinostat'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['SAHA', 'CD'], 'conditions': ["Cushing's Disease"]}, 'referencesModule': {'references': [{'pmid': '14671138', 'type': 'BACKGROUND', 'citation': "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': '16353601', 'type': 'BACKGROUND', 'citation': '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': '16698415', 'type': 'BACKGROUND', 'citation': "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."}], 'seeAlsoLinks': [{'url': 'https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-N-0019.html', 'label': 'NIH Clinical Center Detailed Web Page'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\nCushing 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.\n\nObjective:\n\nTo test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.\n\nEligibility:\n\nPeople 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\n\nDesign:\n\nParticipants will be screened under protocol 03-N-0164.\n\nParticipants will stay in the hospital for 8 days before their surgery.\n\nOn 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.\n\nFor 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.\n\nOn the eighth day, participants will have their surgery. Leftover tissue will be collected for research.\n\nOn the day they are discharged from the hospital, participants will have a physical exam and blood tests.', 'detailedDescription': 'Study Description\n\nThis 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.\n\nObjectives\n\nCushing 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.\n\nPrimary Objective: to determine whether vorinostat reduces midnight plasma ACTH level\n\nSecondary Objectives: to evaluate the effect of vorinostat on urine cortisol levels\n\nEndpoints\n\nPrimary Endpoint: midnight plasma ACTH level on the last day of drug administration. Secondary Endpoints: serum cortisol change during drug administration.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Adult patients (18 years and older)\n* 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.\n* Surgical candidate for resection of ACTH producing pituitary adenoma\n* Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.\n* Able to provide written informed consent at the time of study enrollment.\n* 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.\n\nEXCLUSION CRITERIA:\n\n* Patients who have been previously treated with vorinostat.\n* Patients who have received sellar radiation.\n* Significant medical illnesses that in the investigator s opinion cannot be adequately controlled or would compromise the patient s ability to tolerate this vorinostat.\n* Any history of cancer, unless in complete remission and off of all therapy for that disease for a minimum of 3 years.\n* History of thromboembolic disorder or deep vein thrombosis\n* Presence of abnormal hematological and biochemical parameters, (such as anemia or thrombocytopenia) as defined as:\n\n * Neutrophil count \\< 1.5 K//micro L\n * Hemoglobin \\< 8.0 g/dL.\n * Hematocrit \\< 0.75x LLN (lower limit of normal)\n * RBC count \\< 0.75x LLN\n * Platelet count \\< 100 x 10\\^3 cells/micro L.\n * 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\n * Serum bilirubin level \\> 1.5x ULN.\n* Active infection being currently treated with systemic antibiotics.\n* 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.\n* Pregnancy or lactation.\n* Presence of any disease that will obscure toxicity or dangerously alter drug metabolism (such as uncontrolled diabetes or bleeding disorders)\n* Currently receiving other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat, such as valproate.\n* Currently taking another HDACi, such as valproate.\n* Currently taking coumadin or its derivative anticoagulants.\n* Currently taking any other medication to reduce cortisol or ACTH levels'}, 'identificationModule': {'nctId': 'NCT04339751', 'briefTitle': 'Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': "The Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing's Disease", 'orgStudyIdInfo': {'id': '200019'}, 'secondaryIdInfos': [{'id': '20-N-0019'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'single center, prospective pilot study', 'description': 'effectiveness of vorinostat to reduce midnight ACTH levels in patients with Cushing s Disease', 'interventionNames': ['Drug: Vorinostat']}], 'interventions': [{'name': 'Vorinostat', 'type': 'DRUG', 'description': 'Administration of Vorinostat', 'armGroupLabels': ['single center, prospective pilot study']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'overallOfficials': [{'name': 'Prashant Chittiboina, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Institute of Neurological Disorders and Stroke (NINDS)'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'We do plan to share IPD. we will share all IPD that results in a publication on a public repository, as required by most journals. the data will be de-identified and anonymized.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Neurological Disorders and Stroke (NINDS)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}