Effect of Vorinostat on Nervous System Hemangioblastomas in Von Hippel-Lindau Disease (Missense Mutation Only)

NCT02108002 | Completed Phase 1

• 2 other identifiers: 14006714-N-0067
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Von Hippel-Lindau (VHL) disease is a rare gene disease. People with VHL often have a brain tumor called hemangioblastoma. Standard treatment for these tumors is risky surgery. Researchers want to find new ways to treat people who have the tumors. They want to see if a drug that fights other cancers might slow the growth of hemangioblastomas in some people with VHL. Some people with VHL have mutations that make abnormal proteins. Tumors form in such people because the abnormal protein is broken down quickly. The cancer drug may work in these tumors by preventing breakdown of protein. Objective: \- To study how the drug vorinostat affects hemangioblastomas in people with VHL. Eligibility: \- Adults at least 18 old with hemangioblastomas from VHL. Design:

• Participants must already be in study 03-N-0164. They must have tumor surgery scheduled.
• Participants must stop taking most medications 14 days before surgery.
• One week before surgery, participants will enter the hospital. They will be screened with medical history and physical and neurological exams. They will give blood and urine samples. Participants will have an electrocardiogram. For this test, small sticky patches are put on the arms, legs, and chest. Participants will lie still for a few minutes while a machine records heart rate and rhythm.
• Participants will take one vorinostat by mouth each day for 7 days.
• Participants will have blood drawn during the week to check for any side effects.
• Participants will have their tumor removed in surgery. Researchers will study the tumor tissue for the effects of the study drug.
• A nurse will call participants 1 month after surgery to check for side effects.

Conditions

Von Hippel-Lindau Disease

Keywords

Missense Mutations; Hemangioblastoma; Histone Deacytelase Inhibitors; Von Hippel-Lindau Disease

Outcome Measures

Primary Outcomes (1)

• The presence and quantity of mutant VHL protein in resected hemangioblastoma specimens, including comparison of specimens without vorinostat treatment and those with presurgical vorinostat treatment.

  ongoing

Interventions

Vorinostat DRUG

Eligibility Criteria

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

You may qualify if:

• Adult patients (age greater than or equal to 18 years)
• Known VHL disease arising from a missense mutation.
• Demonstrated clinical progression of CNS hemangioblastoma.
• Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.
• Able to provide written informed consent.

You may not qualify if:

• Patients who have been previously treated with vorinostat.
• Significant medical illnesses that in the investigator s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient s ability to tolerate this therapy.
• History of a second cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
• Active infection or serious concurrent medical illness.
• Pregnancy and breast-feeding.
• Presence of any disease that will obscure toxicity or dangerously alter drug metabolism (such as uncontrolled diabetes, liver disease, bleeding disorder)
• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Harries RW. A rational approach to radiological screening in von Hippel-Lindau disease. J Med Screen. 1994 Apr;1(2):88-95. doi: 10.1177/096914139400100205.

  PMID: 8790493 BACKGROUND

• Friedrich CA. Von Hippel-Lindau syndrome. A pleomorphic condition. Cancer. 1999 Dec 1;86(11 Suppl):2478-82.

  PMID: 10630173 BACKGROUND

• Maher ER, Willatt L, Cuthbert G, Chapman C, Hodgson SV. Three cases of 16q duplication. J Med Genet. 1991 Nov;28(11):801-2. doi: 10.1136/jmg.28.11.801. No abstract available.

  PMID: 1820771 BACKGROUND

• Chittiboina P, Mandal D, Bugarini A, Asuzu DT, Mullaney D, Mastorakos P, Stoica S, Alvarez R, Scott G, Maric D, Elkahloun A, Zhuang Z, Chew EY, Yang C, Linehan M, Lonser RR. Proteostasis Modulation in Germline Missense von Hippel Lindau Disease. Clin Cancer Res. 2023 Jun 13;29(12):2199-2209. doi: 10.1158/1078-0432.CCR-22-3651.

  PMID: 37018064 DERIVED

MeSH Terms

Conditions

von Hippel-Lindau Disease; Hemangioblastoma

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Hemangioma, Capillary; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2014
• First Posted: April 9, 2014
• Study Start: April 5, 2014
• Primary Completion: September 12, 2018
• Study Completion: September 12, 2018
• Last Updated: September 14, 2018

Record last verified: 2018-09-12

Locations

US (1)