Vorinostat and Temozolomide in Treating 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.
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 SAHA with Temozolomide defined as the dose at which less than one-third of patients experience DLT based on the CTC severity grading (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Efficacy in terms of anti-tumor activity based on clinical, radiographic, and biologic assessments (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2005|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral vorinostat once or twice daily on days 1-7 and 15-21 OR once or twice daily on days 1-7. Patients also receive oral temozolomide once daily 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. Patients receive vorinostat and temozolomide as in part 1.
Given orallyDrug: temozolomide
I. Determine the maximum tolerated dose (MTD) of vorinostat in combination with temozolomide in patients with malignant gliomas.
II. Characterize the safety profile of vorinostat in combination with temozolomide in these patients.
I. Characterize the pharmacokinetics of vorinostat (SAHA) in combination with temozolomide in these patients.
II. Determine efficacy of vorinostat (SAHA) in combination with temozolomide as measured by objective response in these patients.
I. Correlate response to treatment with the molecular phenotype of the tumor in these patients.
OUTLINE: This is a 2-part, multicenter, dose-escalation study of vorinostat.
PART 1: Patients receive oral vorinostat once or twice daily on days 1-7 and 15-21 OR once or twice daily on days 1-7. Patients also receive oral temozolomide once daily 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.
Cohorts of 3-6 patients receive escalating doses of vorinostat during course 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
PART 2: Patients receive vorinostat and temozolomide as in part 1*.
[Note: *Beginning in course 2, all patients receive a higher dose of temozolomide.]
Cohorts of 3-6 patients receive de-escalating doses of vorinostat (beginning at the MTD determined in part 1) during courses 1 and 2 until the MTD for part 2 is determined. The MTD is defined as in part 1. An additional 6 patients are treated at the MTD.
After completion of study treatment, patients are followed periodically for survival.
|United States, California|
|University of California at Los Angeles (UCLA )|
|Los Angeles, California, United States, 90095|
|San Francisco, California, United States, 94115|
|United States, Maryland|
|Adult Brain Tumor Consortium|
|Baltimore, Maryland, United States, 21231-1000|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Pennsylvania|
|University of Pittsburgh|
|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)|