Recurrent GBM Treated With Neurosurgical Resection and IORT Using the Xoft Axxent eBx System and Bevacizumab

Inclusion Criteria: 1. Subject has the ability to provide written informed consent 2. Subject has the willingness to comply with all study procedures for the duration of the study 3. Subject has histopathologically proven diagnosis of GBM or variants (gliosarcoma, giant cell glioblastoma etc.). Subjects will be also eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made. 4. Subjects must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced MRI within 21 days prior to enrollment 5. Subjects must have passed an interval of 6 months or greater between completion of prior radiotherapy and enrollment. If subjects have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria: 1. New areas of tumor outside the original radiotherapy fields as determined by the investigator, or 2. Histologic confirmation of tumor through biopsy or resection, or 3. Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and enrollment 6. The recurrent GBM must be potentially-resectable with the intent to resect such that residual tumor rim is less than 1 cm enhancing disease 7. The recurrent GBM must have the appropriate dimensions to allow a Xoft applicator balloon to fit into the tumor cavity 8. Subject has prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent of lower doses. Patients who have received prior treatment with non-standard RT dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible as long as the criterion in 5. is met or approved by principal investigator. 9. Subjects who have undergone CNS related core or needle biopsies, a minimum of 7 days must have elapsed prior to registration 10. History/physical examination, including neurologic examination, within 14 days prior to enrollment (i.e. date the informed consent was signed by the patient) 11. Subject must be ≥ 18 years of age 12. Subject must have a Karnofsky Performance Score ≥ 60% 13. Subject will have had a CBC/differential obtained within 14 days prior to enrollment , with adequate bone marrow function, i.e.: d) Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 e) Platelets ≥ 75,000 cells/mm3 f) Hemoglobin ≥ 9.0 g/dl (The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable.) 14. Subjects liver and renal function test should reflect adequate hepatic and renal function 14 days prior to enrollment, i.e.: 1. Total bilirubin ≤ 2.0 mg/dL, and SGOT or AST ≤ 2.5 times the upper limit of normal 2. Serum creatinine ≤ 1.8 mg/dL) within 14 days prior to enrollment 15. Subject urine protein level must reflect the following requirements within 14 days before enrollment: 1. Urine protein: creatinine (UPC ) ratio \< 1.0 OR 2. Urine dipstick for proteinuria ≤ 2+ (patients who have \> 2+ proteinuria on dipstick urinalysis at baseline, must have an UPC ratio \<1.0 to be eligible. If the UPC ratio is ≥ 1.0, subsequent 24 hrs urine collection must be ≤ 1 g protein in 24 hrs) 16. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: 1. No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices). 2. In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 14 days prior to enrollment. 17. Women of child-bearing potential must have a negative pregnancy test within 7 days of treatment 18. Subjects of child-bearing potential must agree to use adequate contraceptive precautions and not to breastfeed (if applicable) until six months after the end of the treatment with Bevacizumab. 19. Patient is planned to have surgery for recurrent Glioblastoma Exclusion Criteria: 1. Subject has had more than three relapses 2. Subject has multi-centric disease 3. Subject has tumors in or near (less than 10mm from tumor margin) critical brain structures, that would exclude sufficient dose delivery to the tumor margin: 1. Optic Chiasm 2. Optic Nerve 4. Subject has infratentorial, or leptomeningeal evidence of recurrent disease 5. Subject has recurrent or persistent tumor greater than 6 cm in maximum diameter 6. Subject underwent prior therapy with an inhibitor of VEGF or VEGFR (including Bevacizumab) 7. Subject suffered from prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible). 8. Women who are pregnant or nursing. Women with child-bearing potential or sexually active men that are not willing/able to use medically acceptable forms of contraception. 9. Subject has contraindications for MRI with or without gadolinium. 10. Subject has contraindications for anesthesia or surgery. 11. Subject is on another therapeutic clinical trial concurrently. 12. Subject suffers severe, active co-morbidity, defined as follows: 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to enrollment 2. Transmural myocardial infarction within the last 6 months prior to enrollment 3. History of stroke or transient ischemic attack within 6 months prior to enrollment 4. Significant vascular (aortic) disease or clinically significant peripheral vascular disease 5. Active venous or arterial thromboembolic disease 6. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment 7. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment 8. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Laboratory tests for liver function other than screening panel coagulation parameters are not required for entry into this protocol 9. Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. HIV testing is not required for entry into this protocol. 13. Prior history of hypertensive crisis or hypertensive encephalopathy 14. Subject has history of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to enrollment 15. Subject suffers from gastrointestinal bleeding or any other hemorrhage /bleeding event CTCAE v.5 grade 3 or greater within 30 days prior to enrollment 16. Subject suffers from Hypersensitivity to Bevacizumab