Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
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|ClinicalTrials.gov Identifier: NCT00268385|
Recruitment Status : Active, not recruiting
First Posted : December 22, 2005
Last Update Posted : November 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Recurrent Adult Brain Neoplasm||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Temozolomide Drug: Vorinostat||Phase 1|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||83 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas|
|Actual Study Start Date :||December 16, 2005|
|Actual Primary Completion Date :||October 15, 2011|
Experimental: 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.]
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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 ]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.
- Efficacy in terms of anti-tumor activity based on clinical, radiographic, and biologic assessments (Part II) [ Time Frame: Up to 4 years ]A descriptive analysis of evidence of anti-tumor activity will be provided based on clinical, radiographic, and biologic assessments of efficacy.
- Plasma pharmacokinetic parameters of vorinostat [ Time Frame: Baseline, 1, 2, 3, 4, 6, 8, and 24 hours post-dose day 1 of course 1 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00268385
|Principal Investigator:||Patrick Y Wen||National Cancer Institute (NCI)|