Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas

NCT ID: NCT00268385

Last Updated: 2025-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-12-16

Study Completion Date

2026-04-24

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

Conditions

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Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Recurrent Adult Brain Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (vorinostat, temozolomide)

PART 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\*.

\[Note: Beginning in course 2, some patients may receive a higher dose of temozolomide.\]

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Temozolomide

Intervention Type DRUG

Given orally

Vorinostat

Intervention Type DRUG

Given orally

Interventions

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Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Temozolomide

Given orally

Intervention Type DRUG

Vorinostat

Given orally

Intervention Type DRUG

Other Intervention Names

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CCRG-81045 Gliotem Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temizole Temodal Temodar Temomedac TMZ L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick Y Wen

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

National Cancer Institute Neuro-Oncology Branch

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2009-00675

Identifier Type: REGISTRY

Identifier Source: secondary_id

NABTC 04-03

Identifier Type: -

Identifier Source: secondary_id

CDR0000450762

Identifier Type: -

Identifier Source: secondary_id

NABTC04-03

Identifier Type: OTHER

Identifier Source: secondary_id

NABTC-04-03

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA137443

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062399

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00675

Identifier Type: -

Identifier Source: org_study_id

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