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Adult Anaplastic AstrocytomaPhase 1NCT00268385

Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 17 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating patients with malignant gliomas. Drugs used in chemotherapy, such as vorinostat and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
17 sitesUnited States
Study dates
16 Dec 2005to 24 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Patients with histologically proven intracranial malignant glioma will be eligible for this protocol; malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified); patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must have signed an authorization for the release of their protected health information; patients must be registered with the Adult Brain Tumor Consortium (ABTC) Central Office database prior to treatment with study drug
  • Life expectancy > 8 weeks
  • Karnofsky performance status of >= 60
  • White blood cell (WBC) >= 3,000/mm^3
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
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  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 10 g/dL; eligibility level for hemoglobin may be reached by transfusion
  • Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • If liver function tests are above the institutional upper limit of normal but < 2 times institutional upper limit of normal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
  • Creatinine < 1.5 mg/dL
  • A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days; if the steroid dose is increased between the date of imaging and registration a new baseline magnetic resonance (MR)/computed tomography (CT) is required; the same type of scan, i.e., magnetic resonance imaging (MRI) or CT must be used throughout the period of protocol treatment for tumor measurement
  • Patients must have an interval of greater than or equal to 3 weeks (21) days from the completion of radiation therapy to study entry
  • Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 7 days prior to registration; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of participation in the study
  • Patients must be willing to participate in the pharmacokinetic studies
  • ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART I OF THE STUDY
  • Patients with either stable disease after radiation therapy or with progression are eligible (except if they have progressed on temozolomide; patients who have received prior treatment with temozolomide and have stable disease are eligible
  • Patients with recurrent disease may have had treatment for any number of prior relapses; relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy)
  • Patients must have recovered from the toxic effects of prior therapy: 28 days from any investigational agent, 28 days from prior cytotoxic therapy except 23 days from last dose of temozolomide for patients taking the standard 5 days every 28 day regimen of temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration, and 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count); any questions related to the definition of non-cytotoxic agents should be directed to the study chair
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
  • They have recovered from the effects of surgery
  • Residual disease following resection is not mandated for eligibility into the study; to best assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration; if the 96-hour scan is more than 14 days before registration, the scan needs to be repeated; if the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days
  • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy or surgical documentation of disease
  • ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART II OF THE STUDY
  • Only patients with stable disease after radiation therapy are eligible for part 2 of the study; patients with recurrent disease are ineligible
  • The only prior therapy permitted for patients in part 2 of the study is concomitant temozolomide with radiation therapy or radiation therapy alone; patients that are stable on adjuvant temozolomide may also participate
  • Patients with recurrent disease and prior chemotherapies (except concurrent or adjuvant temozolomide) will not be included in this part of the study

Who cannot join

  • Patients who have progressed on temozolomide are ineligible
  • Patients must not have any 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; patients with a history of any other 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 are ineligible
  • Patients must not have active infection or serious intercurrent medical illness
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat (SAHA); potential risks may also apply to temozolomide
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
  • Patients who are known to be human immunodeficiency virus (HIV) positive and are receiving combination antiretroviral therapy are ineligible
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  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in study
  • Patients should not have taken valproic acid (another histone deacetylase inhibitor) for at least 2 weeks prior to enrollment

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • National Cancer Institute Neuro-Oncology Branch

    Bethesda, Maryland, 20892

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas

This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating patients with malignant gliomas. Drugs used in chemotherapy, such as vorinostat and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug. Giving vorinostat together with temozolomide may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of vorinostat (suberoylanilide hydroxamic acid [SAHA]) in combination with temozolomide in patients with malignant gliomas.

II. To characterize the safety profile of vorinostat (SAHA) in combination with temozolomide.

SECONDARY OBJECTIVES:

  1. To characterize the pharmacokinetics of vorinostat (SAHA) in combination with temozolomide.

II. To determine efficacy of vorinostat (SAHA) in combination with temozolomide as measured by objective response.

TERTIARY OBJECTIVES:

  1. To explore the association of response to treatment to the molecular phenotype of the tumor.

II. To assess the effects of vorinostat (SAHA) on histone acetylation status in peripheral mononuclear cells.

OUTLINE: This is a 2-part, dose-escalation study of vorinostat.

PART I: Patients receive vorinostat orally (PO) once (QD) or twice daily (BID) on days 1-7 and 15-21 OR QD or BID on days 1-7. Patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Beginning in course 2, some patients may receive a higher dose of temozolomide. Treatment may continue beyond 13 courses at the discretion of the investigator.

PART II: Patients receive vorinostat and temozolomide as in part 1*.

[Note: *Beginning in course 2, all patients receive a higher dose of temozolomide.]

After completion of study treatment, patients are followed up periodically.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Temozolomide, Vorinostat
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Glioma, Brain Neoplasms

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    Given orally

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given orally

Study groups in NCT00268385
Study groupRoleWhat they receive
Treatment (vorinostat, temozolomide)ExperimentalPART I: Patients receive vorinostat PO QD or BID on days 1-7 and 15-21 OR QD or BID on days 1-7. Patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Treatment may continue beyond 13 courses at the discretion of the investigator. PART II: Patients receive vorinostat and temozolomide as in part I*. [Note: Beginning in course 2, some patients may receive a higher dose of temozolomide.]
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temozolomide; Drug: Vorinostat

What is being measured

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

  1. MTD of vorinostat with temozolomide defined as the dose at which less than one-third of patients experience dose-limiting toxicity based on the CTC severity grading (Part I)

    For both parts of the study, treatment administration will be described for all cycles. Doses administered, dose modifications/delays, and duration of therapy will be evaluated. Safety variables summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Distribution by CTC severity grade (when applicable) and clinical relevance will be given.

    Measured: 28 days

Secondary outcomes (2)

  1. Efficacy in terms of anti-tumor activity based on clinical, radiographic, and biologic assessments (Part II)

    A descriptive analysis of evidence of anti-tumor activity will be provided based on clinical, radiographic, and biologic assessments of efficacy.

    Measured: Up to 4 years

  2. Plasma pharmacokinetic parameters of vorinostat

    Presented in tabular and graphic form. Pharmacokinetic parameters of interest such as maximal plasma concentration (Cmax), time of maximal concentration (Tmax), area under the plasma concentration-time curve (AUCo-t and AUC-infinity), clearance (CL), apparent volume of distribution at steady state (Vdss), terminal half-life (t1/2), and tumor to plasma (whole blood) concentration ratio will be determined using non-compartmental methods. Dose proportionality in pharmacokinetic parameters will be determined by performing a one-way analysis of variance (ANOVA) on dose-normalized parameters.

    Measured: Baseline, 1, 2, 3, 4, 6, 8, and 24 hours post-dose day 1 of course 1

Timeline

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

  1. First posted22 Dec 2005 (estimated)
  2. Study start16 Dec 2005
  3. Primary completion18 Oct 2018
  4. Study completion24 Apr 2027 (estimated)

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00268385
Sponsor's protocol ID
NCI-2009-00675
Other IDs
NCI-2009-00675, NABTC 04-03, CDR0000450762, NABTC04-03, NABTC-04-03, U01CA137443, U01CA062399
Status last verified
Aug 2026
First submitted
20 Dec 2005
Last updated
20 Aug 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 17 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 29 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: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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 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?

This study is still under way. Results are not available in the source record yet.

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?

MTD of vorinostat with temozolomide defined as the dose at which less than one-third of patients experience dose-limiting toxicity based on the CTC severity grading (Part I) (time frame: 28 days). 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 NCT00268385.

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 20 Aug 2026.

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