This phase I trial studies the side effects and best dose of alisertib when combined with fractionated stereotactic radiosurgery in treating patients with high-grade gliomas that have returned after previous treatment with radiation therapy (recurrent). Alisertib may stop the growth of tumor cells by blocking an enzyme needed for the cells to divide. Radiation therapy uses high energy x rays to kill tumor cells. Stereotactic radiosurgery uses special positioning equipment to send a single high dose of radiation directly to the tumor and cause less damage to normal tissue. Delivering stereotactic radiosurgery over multiple doses (fractionation) may cause more damage to tumor tissue than normal tissue while maintaining the advantage of its accuracy.
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of the study treatment. II. To determine the maximum tolerated dose (MTD) of daily oral alisertib when combined with fractionated stereotactic radiation treatment for recurrent high grade glioma. SECONDARY OBJECTIVES: I. To estimate 6 month progression free survival rate. II. To estimate the median time to progression. III. To estimate overall survival. IV. To estimate the impact on quality of life (QoL). OUTLINE: This is a dose-escalation study of alisertib. CONCURRENT PHASE: Patients undergo fractionated stereotactic radiosurgery once daily (QD) every weekday for 10 days and receive alisertib orally (PO) twice daily (BID) concurrently with radiation therapy for 10 days. MAINTENANCE PHASE: Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4-6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Undergo hyperfractionated radiation therapy
Undergo stereotactic radiosurgery
Given PO
Ancillary studies
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Maximum Tolerated Dose (MTD) of Alisertib
Defined as the dose at which \>= 2 patients experience dose-limiting toxicity, graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Up to 30 days after completion of radiation therapy
Number of Participants With Complete or Partial Response
95% confidence intervals will be computed. Response was defined by the Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Work Group (RANO)
Time frame: Up to 5 years
Number of Participants With Progression Free Survival at 6 Months
Estimated through the Kaplan-Meier method.
Time frame: At 6 months
Number of Participants With Overall Survival at 6 Months
Estimated through the Kaplan-Meier method.
Time frame: At 6 months
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