Post-operative Adjuvant Therapy w/wo GammaTile + Systemic Therapy

Inclusion Criteria

• •1. Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
• •2. History of a histopathologically and molecularly confirmed glioblastoma, per Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (c-IMPACT-NOW) criteria ("diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, World Health Organization \[WHO\] grade IV"; this requires presence of amplification of EGFR, whole chromosome 7 gain AND whole chromosome 10 loss, or Telomerase reverse transcriptase (TERT) promoter mutation.
• •3. Patients for which bevacizumab or lomustine are reasonable systemic treatments following surgery.
• •4. Eligible patients must be experiencing a known or suspected first recurrence of a supratentorial GBM following prior first-line concurrent TMZ and RT (allowed hypofractionation of prior RT dose ≥ 40 Gray \[Gy\] of a planned 60 Gy dose) and at least one cycle of adjuvant TMZ. RT must have concluded \>45 days prior to enrollment, and most recent adjuvant TMZ treatment(s) must have been concluded or terminated \>10 days prior to enrollment. Prior adjuvant TMZ cycles up to 12, prior adjuvant tumor-treating fields (TTF), and prior External Beam Radiotherapy (EBRT) doses via proton or photon treatments up to 72 Gy equivalent are allowed. Note: This includes infratentorial recurrences of tumors that were supratentorial at diagnosis. Tumors the were infratentorial at diagnosis are excluded.
• •5. Eligible tumors are defined as the following:
• •1. Supratentorial
• •2. A bi-dimensionally measurable lesion of at least 10 mm, visible on two or more axial slices 5 mm apart.
• •3. The pre-operative tumor (including enhanced and unenhanced tumor) planned for resection that is 60 mm2 or less in maximum cross section.
• •4. Tumor that in the opinion of the enrolling neurosurgeon is amenable to attempted gross total resection (GTR). Prior diagnostic biopsy allowed.
• •5. Anticipated GammaTile placement (i.e., closest aspect of post resection tumor bed that is anticipated to receive GammaTile placement) that is \> 15mm from the optic chiasm or brainstem.
• •6. Multifocal enhancing disease is allowed if it can be fully encompassed in one operative bed while meeting criterion a-e.
• •6. Ability to complete an MRI of the head with and without contrast, and a non-contrast CT.
• •7. All subjects fluent in English will complete neurocognitive evaluations. Patients not fluent in English are allowed on trial but will not take neurocognitive tests as comparative data is only available from tests in the English language.
• •8. Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available from any prior GBM tumor specimen; results of routinely used methods for MGMT methylation testing (e.g., mutagenically separated polymerase chain reaction \[MSPCR\] or quantitative polymerase chain reaction \[PCR\]) are acceptable and results can be from a local lab or central lab used by a prior study.
• •9. Suspicion of suspected tumor recurrence is on imaging and/or histologic grounds. If imaging, at a minimum a contrast-enhanced MRI scan ≤21 days prior to registration (at the time of randomization) should meet Response Assessment in Neuro-Oncology (RANO) criteria.
• •10. Concomitant systemic or local anti-cancer medications or treatments, other than those on this protocol, are prohibited in this study in the absence of progression.
• •11. Patients can be on a stable or decreasing dose of steroids for 1 week before the screening MRI. Utilization of the lowest useful dose and shortest useful course are encouraged.
• •12. Karnofsky Performance Scale (KPS) score of ≥ 70 documented within ± 21 days of signing consent.
• •13. Eastern Cooperative Oncology Group Performance Score (ECOG-PS) of \<2 documented ≤ 21 days of signing consent.
• •14. Blood test results ≤ 21 days prior to surgery (can be re-run prior to surgery):
• •1. Leukocytes ≥ 2,500/mm3
• •2. Absolute neutrophil count ≥ 1,500/mm3
• •3. Absolute lymphocyte count ≥ 800/mm3
• •4. Platelets ≥ 75,000/mm3
• •5. Hemoglobin ≥ 8 g/dL
• •6. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled)
• •7. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])
• •* 2.5 x ULN
• •8. Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x ULN
• •9. Alkaline phosphatase ≤ 2.5 x ULN
• •10. Creatinine clearance ≥ 50 mL/min/1.73 m2 by Cockcroft-Gault
• •15. Women of childbearing potential must have a negative serum or urine pregnancy test ≤7 days prior to randomization. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period. They must be willing to use a form of contraception to prevent pregnancy during treatment.
• •16. Willingness and ability to provide written informed consent or have their legally authorized representative provide consent and Health Insurance Portability and Accountability (HIPAA) authorization for them if they physically are unable to sign prior to performance of any study-related procedure.
• •17. Availability of prior radiotherapy treatment plan details in Digital Imaging and Communications in Medicine (DICOM) format is desired but not required for study participation.