"Mathematical Model-Adapted Radiation fractionation Schedule for patients with recurrent Glioblastoma (MARS-Glio)"

This research study is studying a new schedule of radiation therapy for recurrent
glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on
a new model for radiation resistance in glioblastoma.

The name of the radiation schedule involved in this study is:

- Re-irradiation for glioblastoma using a novel Mathematical Model-Adapted Radiation
Fractionation Schedule

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.