This study is being done to determine if an investigational cancer treatment called vorinostat combined with fractionated stereotactic radiation therapy (FSRT) is effective in treating recurrent high grade gliomas. The main goal of this research study is to determine the highest dose of vorinostat that can be given to patients with recurrent tumors. The study will also determine the potential side effects and safety of these treatment combinations. Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors help unravel the deoxyribonucleic acid (DNA) of the cancer cells and make them more susceptible to the treatment with radiation.
PRIMARY OBJECTIVES: I. To determine the phase II dose when intermittent short-course vorinostat is combined with fractionated radiation therapy in recurrent high-grade glioma. SECONDARY OBJECTIVES: I. Define the pharmacokinetics of vorinostat entry into the cerebrospinal fluid (CSF) and demonstrate that vorinostat influences glioma biology. OUTLINE: This is a dose-escalation study of vorinostat. Patients receive high-dose vorinostat orally (PO) at 48, 27, and 3 hours prior to surgery. Beginning 2-6 weeks later, patients receive vorinostat PO once daily (QD) on days 1-3 in weeks 1-2and undergo fractionated stereotactic body radiation therapy on days 1-5 in weeks 1-2. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given PO
Undergo fractionated stereotactic radiation therapy
Correlative studies
Correlative studies
Undergo neurosurgery
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Maximal tolerated dose (MTD), defined as one level below at which 2 of 6 patients experience a dose-limiting toxicity (DLT)
Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.
Time frame: 48 hours
Dose limiting toxicities (grade 3 or higher) defined by Common Toxicity Criteria (CTC) version 4.0
Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.
Time frame: 48 hours
Overall survival (OS)
Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.
Time frame: Up to 2 years
Progression free survival (PFS)
Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.
Time frame: Time from start of treatment to time to progression, up to 2 years
Response rate defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Analysis of study data will be descriptive. A 2-sided exact 95% confidence interval of response rate will be computed.
Time frame: Up to 2 years
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