Clinical Trial: Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Study of Alisertib With Concurrent Fractionated Stereotactic Radiation Treatment for Recurrent High Grade Gliomas

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Maximum tolerated dose (MTD) of alisertib [ Time Frame: Up to 30 days after completion of radiation therapy ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of patients at the MTD with complete or partial response [ Time Frame: Up to 5 years ]
    95% confidence intervals will be computed
  • Progression free survival among patients at the MTD based on brain magnetic resonance imaging and defined according to updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology Work Group [ Time Frame: At 6 months ]
    Estimated through the Kaplan-Meier method.
  • Overall survival among patients at the MTD [ Time Frame: Up to 5 years ]
    Estimated through the Kaplan-Meier method.


Original Secondary Outcome: Same as current

Information By: Thomas Jefferson University

Dates:
Date Received: July 7, 2014
Date Started: January 2015
Date Completion:
Last Updated: October 19, 2016
Last Verified: October 2016