Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
A Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas
7 other identifiers
interventional
83
1 country
17
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2005
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 16, 2005
CompletedFirst Submitted
Initial submission to the registry
December 20, 2005
CompletedFirst Posted
Study publicly available on registry
December 22, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 18, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 24, 2027
ExpectedMay 7, 2026
February 1, 2026
12.8 years
December 20, 2005
May 6, 2026
Conditions
Outcome Measures
Primary Outcomes (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.
28 days
Secondary Outcomes (2)
Efficacy in terms of anti-tumor activity based on clinical, radiographic, and biologic assessments (Part II)
Up to 4 years
Plasma pharmacokinetic parameters of vorinostat
Baseline, 1, 2, 3, 4, 6, 8, and 24 hours post-dose day 1 of course 1
Study Arms (1)
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\*. \[Note: Beginning in course 2, some patients may receive a higher dose of temozolomide.\]
Interventions
Given orally
Given orally
Eligibility Criteria
You may qualify if:
- 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
- +14 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Cancer Institute Neuro-Oncology Branch
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patrick Y Wen
National Cancer Institute (NCI)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2005
First Posted
December 22, 2005
Study Start
December 16, 2005
Primary Completion
October 18, 2018
Study Completion (Estimated)
April 24, 2027
Last Updated
May 7, 2026
Record last verified: 2026-02