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High Grade GliomasPhase 2NCT00302159

Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

A Phase 2 study testing adjuvant therapy, Temozolomide and Valproic Acid in people with High Grade Gliomas and Brain Tumors, run by National Cancer Institute (NCI) at 3 sites 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: Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas. The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
High Grade Gliomas, Brain Tumors
What is being tested?
adjuvant therapy, Temozolomide and Valproic Acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
3 sitesUnited States
Study dates
Mar 2006to Nov 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological diagnosis:
  • Pathologically confirmed glioblastoma multiforme.
  • Histologic diagnosis of glioblastoma multiforme (GBM) will have been established by biopsy or resection no more than 6 weeks prior to enrollment.
  • The patient is a candidate for definitive external beam radiotherapy.
  • Patients must be older than 18 years with a life expectancy greater than 8 weeks.
  • Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
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  • Patients must have a primary medical oncologist in the community who is willing to collaborate with the Radiation Oncology Branch (ROB) staff in the clinical management of the patient, specifically in the prescription of Temozolomide and toxicity monitoring in the adjuvant phase.
  • Laboratory functions:
  • Adequate bone marrow function defined as a peripheral absolute granulocyte count of greater than 1500/mm^3, hemoglobin greater than 10gm/dL, and platelet count greater than 100,000/mm^3.
  • Adequate liver function, defined as bilirubin and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 2 x the upper limit of normal.
  • Serum creatinine less than 1.5 mg/dl.
  • Serum albumin greater than 0.75 x normal.
  • All patients or their legal guardian must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any of the protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).
  • Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Who cannot join

  • Prior therapy:
  • Patients who have previously received valproic acid.
  • Patients who have previously received radiation therapy to the brain.
  • Patients who have received chemotherapy for the treatment of their high grade glioma or who are currently receiving other investigational chemotherapeutic agents.
  • Patients with a known history of disorders of urea metabolism.
  • Concurrent therapy:
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  • The concurrent use of sulfamethoxazole, salicylates or naproxen is not allowed.
  • Patients with a history of or concurrent second malignancy other than non-melanoma skin cancer or cervical cancer less than 3 years since GBM diagnosis.
  • Pregnant or breast-feeding females are excluded because of the potential mutagenic effects on a developing fetus or newborn.
  • Clinically significant unrelated systemic illness which in the judgement of the Principal or Associate Investigator would compromise the patient's ability to tolerate this therapy or are likely to interfere with the study procedures or results, including but not limited to Insulin dependent diabetes.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104-6056

  • Virginia Commonwealth University

    Richmond, Virginia, 23284

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination With Temodar and Radiation Therapy in Patients With High Grade Gliomas: Multi-Institutional Trial

Background:

  • Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas.
  • The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells.
Read more

Objectives:

-To determine the effectiveness of adding valproic acid to standard treatment with radiation therapy and temozolomide for treating glioblastoma.

Eligibility:

-Patients 18 years of age and older with glioblastoma multiforme who have not been previously treated with chemotherapy of radiation.

Design:

  • This Phase II trial will enroll 41 patients.
  • Patients will receive radiation therapy to the brain once a day, Monday through Friday, for 6 1/2 weeks.
  • Patients will take temozolomide once a day by mouth, Monday through Friday, during the period of radiation treatment. Starting 4 weeks after radiation therapy, patients will take temozolomide once a day for 5 days every 28 days for a total of six cycles.
  • Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the first day of radiation therapy and continuing until the completion of chemotherapy and radiation therapy.
  • Patients will have follow-up visits 1 month after completing therapy, then every 3 months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical examination, blood tests and magnetic resonance imaging of the brain.
Read the detailed description

BACKGROUND:

  • Histone deacetylase inhibitors (HDACi) have recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo.
  • Valproic acid has also recently been demonstrated to be a potent HDAC.
  • Valproic acid has a long clinical history in patients with and without brain tumors and is known to cross the blood-brain barrier. However, the use of valproic acid in combination with temozolomide and radiotherapy for patients with high-grade gliomas has never been tested.

OBJECTIVES:

-The primary measure of efficacy will be progression free survival and overall survival.

ELIGIBILITY:

  • Patients greater than 18 years old
  • Diagnosis glioblastoma multiforme
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Patients who have not been previously treated with chemotherapy or radiation

DESIGN:

  • This is a Phase II trial to determine the efficacy of valproic acid in combination with external beam radiation therapy and temozolomide in patients with high-grade gliomas.
  • Patients will be treated with external beam radiation therapy in a standard manner with temozolomide given daily during the radiation. The valproic acid will be administered daily beginning one week prior to the first day of irradiation and continuing until the completion of chemoradiation.
  • We anticipate that accrual to this trial of 41 patients will take approximately 1 year.
Being tested
adjuvant therapy, Temozolomide, Valproic Acid, Radiation therapy
Keywords
Chemotherapy, Radiation, Brain Tumor, GBM, Radiosensitizer, Glioblastoma, Glioblastoma Multiforme
Medical subject headings
Brain Neoplasms, Glioblastoma

What participants receive

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

  • adjuvant therapyProcedure or surgery

  • TemozolomideDrug

    Also called Temodar

    Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation.

  • Valproic AcidDrug

    Also called Depakote

    Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

  • Radiation therapyRadiation

    External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Study groups in NCT00302159
Study groupRoleWhat they receive
Valproic AcidExperimentalOrally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
Receives: Procedure: adjuvant therapy; Drug: Temozolomide; Drug: Valproic Acid; Radiation: Radiation therapy

What is being measured

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

  1. Median Progression Free Survival.

    Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

    Measured: up to 51 months

  2. Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months

    Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

    Measured: 6, 12, and 24 months

  3. Number of Participants With Best Response

    Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a >50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a >25%, but <50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).

    Measured: up to 63.8 months

  4. Median Overall Survival

    Survival is the interval from the initiation of treatment on protocol to date of death.

    Measured: up to 63.8 months

  5. Percentage of Participants With Overall Survival at 6, 12, and 24 Months

    Percentage of participants who were alive at 6, 12, and 24 months.

    Measured: 6, 12, and 24 months

Secondary outcomes (1)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: 6 years, 7 months and 27 days

Timeline

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

  1. First posted13 Mar 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionJun 2013
  4. Study completionNov 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00302159
Sponsor's protocol ID
060112
Other IDs
06-C-0112
Status last verified
Jul 2016
First submitted
11 Mar 2006
Last updated
18 Aug 2016
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Davis FG, McCarthy BJ, Freels S, Kupelian V, Bondy ML. The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data. Cancer. 1999 Jan 15;85(2):485-91.

    PubMed 10023719

  • Loeffler JS, Alexander E 3rd, Shea WM, Wen PY, Fine HA, Kooy HM, Black PM. Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol. 1992 Sep;10(9):1379-85. doi: 10.1200/JCO.1992.10.9.1379.

    PubMed 1325539

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing adjuvant therapy, Temozolomide and Valproic Acid in people with High Grade Gliomas and Brain Tumors, run by National Cancer Institute (NCI) at 3 sites 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 14 inclusion and 10 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 18 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Median Progression Free Survival. (time frame: up to 51 months). The study lists 5 primary outcomes in all. 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 NCT00302159, which also lists 2 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 18 Aug 2016; AzTrials last refreshed its copy on 8 Nov 2026.

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