⁃ A. Recurrent glioblastoma (or variants such as gliosarcoma) based on one of the following criteria:

• An area of MRI enhancement consistent with glioblastoma outside of the initial high dose radiation field.

• Biopsy or resection proven recurrent glioblastoma.

• Progressive glioblastoma based on advanced imaging (brain positron emission tomography (PET), perfusion MRI, or clinical MR Spectroscopy)

⁃ B. Pathology diagnosis of glioblastoma, or variants such as gliosarcoma, on initial and/or reresection by 2021 WHO glioblastoma criteria. Prior pathology reports or specimens can be reexamined and reclassified as glioblastoma based on current criteria.

⁃ C. Total area of recurrence on T1 post-contrast MRI (including all nodules of likely tumor) have a linear maximum measurement of 6 cm or less.

⁃ D. Patients must have received prior brain radiation therapy for glioma in conventional fractionation (1.8 - 2 Gy per fraction, total dose maximum 63 Gy).

⁃ E. Patients must have completed prior brain radiation four to six months or more prior to study treatment for recurrent tumors that are at least half based within the high dose (\> 46 Gy) radiation field.

• For marginal or out of field radiation failures where at least half of the enhancing disease is outside of the prior high dose radiation field but there is field overlap, patients must have completed prior radiation at least four months or more prior to study treatment.

• For in field radiation failures where at least half of the enhancing disease is within the prior high dose radiation field, patients must have completed prior radiation at least six months or more prior to study treatment.

⁃ F. A minimum time must be elapsed from the administration of any prior anti-tumor or investigational agents to initiation of study treatments on this protocol as follows:

• 28 days or 5 half-lives, whichever is shorter, elapsed from the administration of any experimental agent prior to initiation of study treatment.

• 28 days elapsed from the administration of any prior cytotoxic agents except

⁃ i. 14 days from vincristine and ≥ 21 days from procarbazine and Temozolomide (TMZ) prior to initiation of study treatment.

⁃ G. Age at least 18.

⁃ H. Patients must be able to have MRI scans.

⁃ I. Patient must be able to provide written informed consent.

⁃ J. ECOG performance status 0-2.

⁃ K. Life expectancy greater than 12 weeks at the discretion of the enrolling investigator.qa

⁃ L. Female subjects should have a negative serum pregnancy test unless they confirm their menopausal status and/or have undergone previous hysterectomy and/or oophorectomy.

⁃ M. Both men and women with childbearing potential should agree to use effective contraception for the duration of the treatment and for at least 6 months after the last treatment since medications that will be used can be harmful for the embryo. See contraception requirements, protocol section 4.16.

⁃ N. Complete blood count (CBC)/differential within 21 days prior to registration with absolute neutrophil count at least 1500 cells/mm2, platelets at least 75,000 cells/mm2, and hemoglobin at least 9.0 g/dl (transfusion or other intervention to achieve Hgb of 9.0 or greater is acceptable).

⁃ O. Liver function tests must demonstrate total bilirubin 2 mg/dL or less, serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal or less within 21 days prior to registration.

⁃ P. Kidney function tests must indicate serum creatinine 1.8 mg/dL or less within 21 days prior to registration and the following:

⁃ a. Urine protein: creatinine (UPC) ratio \< 1.0 within 14 days prior to registration OR urine dipstick for proteinuria ≤ 2+ (patients discovered to have \> 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is \<1.0 to be eligible. If the UPC ratio is ≥ 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible).

⁃ i. Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas:

• \[urine protein\]/\[urine creatinine\]: if both protein and creatinine are reported in mg/dL

• \[(urine protein) x0.088\]/\[urine creatinine\]: if urine creatinine is reported in mmol/L

⁃ Q. Patients on full-dose anticoagulants must meet both of the following criteria:

• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• In-range international normalized ratio (INR) (typically 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 21 days prior to registration