Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
|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|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas|
- 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.
|Actual Study Start Date:||December 16, 2005|
|Primary Completion Date:||October 15, 2011 (Final data collection date for primary outcome measure)|
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
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Temozolomide
Other Names:Drug: Vorinostat
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268385
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center|
|Birmingham, Alabama, United States, 35233|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|UCSF Medical Center-Mount Zion|
|San Francisco, California, United States, 94115|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|National Cancer Institute Neuro-Oncology Branch|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania/Abramson Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Patrick Wen||National Cancer Institute (NCI)|