Mathematical Model-Adapted Radiation In Glioblastoma

This research study is a Feasibility Study, which means that this is the first time that
investigators are examining this new radiation schedule for recurrent glioblastoma.

- The FDA (the U.S. Food and Drug Administration) has approved radiation therapy as a
treatment option for your disease.

- This is the first time that this particular radiation schedule will be tested in humans.
There many other studies which have tested different radiation schedules in
glioblastoma.

In this research study, investigators are adapting a standard two-week schedule of radiation
commonly used for recurrent glioblastoma using a mathematical model. This study uses the same
total dose of radiation as standard treatments but breaks up the dose into different amounts
daily to maximize tumor kill. investigators have used a new mathematical model to create this
schedule of radiation. This model was created to better represent how glioblastoma cells can
escape the damaging effects of radiation. Based on the results of several laboratory studies,
it is possible that this model may result in improved outcomes compared to standard radiation
schedules.

The primary question of this study is to see whether participants can complete this new
radiation schedule at the scheduled times. In addition, investigators will follow
participants to ensure that this treatment is safe. If this treatment proves feasible,
investigators hope to compare this treatment directly with standard radiation schedules for
newly diagnosed and recurrent glioblastoma.

Inclusion Criteria:

- Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain
imaging with CT or MRI, after prior receipt of definitive therapy including
neurosurgical biopsy or resection and radiation therapy with or without systemic
therapy.

- Participants must be deemed appropriate candidates for re-irradiation

- Histopathologic confirmation of disease as part of routine clinical care is required
either at the time of initial diagnosis and/or at the time of recurrent disease. There
is no requirement for central pathologic review.

- Age ≥ 18 years at the time of enrollment

- Karnofsky Performance Status (KPS) of at least 70

- Exclusion Criteria

- Participants who have received more than one prior course of radiotherapy to the local
site of progressive disease

- Participants who have received prior radiotherapy to the local site of progressive
disease within < 3 months of the anticipated start of re-irradiation

- Participants with recurrent tumor extensively abutting or involving the optic
structures or brainstem, as assessed by the treating radiation oncologist

- Participants without a definable tumor cavity on MRI or CT obtained at study
enrollment

- Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU,
vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab,
nivolumab); however, participants may receive sequential chemotherapy before or after
radiation without limitation. Participants may receive concurrent corticosteroid
and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.