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Von Hippel-Lindau DiseasePhase 1NCT02108002

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

A Phase 1 study testing Vorinostat in people with Von Hippel-Lindau Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Von Hippel-Lindau Disease
What is being tested?
Vorinostat
How many people
7 participants
Where
1 siteUnited States
Study dates
5 Apr 2014to 12 Sep 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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.
Read more

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.
Read the detailed description

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.

Design

We intend to conduct a pilot study with vorinostat in six patients with hemangioblastomas causing significant symptoms from tumor growth. Vorinostat will be administered if the patients are deemed surgical candidates. Patients will receive one (1) dose of 400 mg of vorinostat daily for seven (7) days prior to surgery. On the day of surgery, the patients will not receive vorinostat. Patients will undergo surgery as usual, with no change in planning or technique of the procedure. The tumor specimens from surgery will be examined for presence and quantity of mutant VHL protein. Comparisons for levels of mutant VHL protein will be made with tissue banked from previous surgical resections under 03-N-0164. Measurements of genetic expression of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) will also be performed on these specimens.

Outcome Measures

  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.
  2. Measurement of VEGF and EPO results from resected hemangioblastoma specimens, including comparison of specimens without vorinostat treatment and those with presurgical vorinostat treatment.
Being tested
Vorinostat
Keywords
Missense Mutations, Hemangioblastoma, Histone Deacytelase Inhibitors, Von Hippel-Lindau Disease
Medical subject headings
von Hippel-Lindau Disease, Hemangioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: ongoing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2014 (estimated)
  2. Study start5 Apr 2014
  3. Primary completion12 Sep 2018
  4. Study completion12 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02108002
Sponsor's protocol ID
140067
Other IDs
14-N-0067
Status last verified
12 Sep 2018
First submitted
5 Apr 2014
Last updated
14 Sep 2018
Results posted
No

Publications

  • 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.

    PubMed 8790493

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

    PubMed 10630173

  • 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.

    PubMed 1820771

  • 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.

    PubMed 37018064

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vorinostat in people with Von Hippel-Lindau Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: ongoing). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02108002, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2018.

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