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

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Pilot Study of the Effect of Vorinostat on Nervous System Hemangioblastomas In Von Hippel-Lindau Disease

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
  

  Detailed Summary:

  Background

  Central Nervous System (CNS) hemangioblastomas are the most common tumor found in the familial neoplasia syndrome, Von Hippel-Lindau (VHL).

  Hemangioblastomas cause significant morbidity and mortality. While surgical resection is the treatment of choice for CNS hemangioblastomas, it is associated with morbidity and death. There is a critical need for new non-invasive treatments of VHL-associated CNS hemangioblastomas.

  Vorinostat is a histone deacetylase inhibitor (HDACi) that is FDA-approved for the treatment of refractory cutaneous T-cell lymphoma (CTCL). Vorinostat has been tested in other hematologic malignancies and solid tumors. Recent data suggests that vorinostat may have a potent therapeutic effect in the treatment of VHL-associated hemangioblastomas in patients with missense germline mutations of the VHL gene. In most VHL mutation types, the abnormal VHL protein content is not active, which leads to tumor formation and growth. In missense mutation VHL disease, tumor cells contain a malformed VHL protein that is partially active. However, the protein is degraded quickly by normal cellular mechanisms. Vorinostat prevents degradation of a malformed protein within the tumors. Increased protein leads to slower growth in these tumors.

  Objective

  To determine whether vorinostat reduces degradation of mutant VHL protein in VHL patients with germline missense mutations.

  Eligibility

  Adult patients (age greater than or equal to 18 years) with a known germline missense VHL gene mutation that require surgical resection of a hemangioblastoma.

  Same as current
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: April 5, 2014
  Date Started: March 5, 2014
  Date Completion: December 31, 2018
  Last Updated: May 12, 2017
  Last Verified: December 5, 2016