Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma

Inclusion Criteria

• •Histopathologically proven diagnosis of glioblastoma, OR molecular diagnosis of 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 TERT promoter mutation)
• •Tumor that is in first recurrence following prior first-line radiation therapy (prior dose \>= 40 Gy)
• •* Note: Prior temozolomide, prior tumor-treating fields, and/or Gliadel wafers (if placed at initial tumor resection) are allowed, but none of these are required
• •Unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan within 21 days prior to registration
• •Per radiation oncologist review of MRI within 21 days prior to registration, must have focus of progressive, contrast-enhancing tumor that is amenable to FSRT, defined as the following:
• •* At least 1 cm x 1 cm contrast-enhancing tumor that is no greater than 4 cm in largest dimension
• •* FSRT target is at least 0.5 cm from the optic chiasm and brainstem
• •* Note, multifocal disease (i.e., other sites of tumor beyond the tumor being targeted for FSRT) is allowed if the above criteria are met for the tumor that is the proposed target for FSRT
• •Surgical cohort only (Phase II only):
• •* Must be a candidate for repeat surgery (significant debulking or gross total resection of the contrast enhancing area) as determined by the neurosurgeon or multidisciplinary team
• •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)
• •The following intervals from previous treatments to registration are required to be eligible:
• •* If prior radiation was \< 60 Gy, an interval of at least 12 weeks (84 days) must have elapsed since the completion of radiation therapy
• •* If prior radiation was \>= 60 Gy, an interval of least 6 months (182 days) must have elapsed since the completion of radiation therapy, unless the target lesion for FSRT is outside of the 80% isodose line of the original radiation plan
• •* At least 21 days from temozolomide
• •* At least 28 days from any investigational (not Food and Drug Administration \[FDA\]-approved for glioblastoma) agents, or within a time interval less than at least 5 half-lives of the investigational agent whichever is shorter (Note: anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or pathway-targeting agents are not allowed)
• •Age \>= 18 years
• •Karnofsky performance status \>= 70 within 14 days prior to registration
• •History/physical examination within 14 days prior to registration
• •Leukocytes \>= 2,500/mm\^3 (within 14 days prior to registration)
• •Absolute neutrophil count \>= 1,500/mm\^3 (within 14 days prior to registration)
• •Absolute lymphocyte count \>= 800/mm\^3 (within 14 days prior to registration)
• •Platelets \>= 100,000/mm\^3 (within 14 days prior to registration)
• •Hemoglobin \>= 8 g/dL (within 14 days prior to registration)
• •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) (within 14 days prior to registration)
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN (within 14 days prior to registration)
• •Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x ULN (within 14 days prior to registration)
• •Alkaline phosphatase =\< 2.5 x ULN (within 14 days prior to registration)
• •Creatinine clearance \>= 30 mL/min/1.73 m\^2 by Cockcroft-Gault (within 14 days prior to registration)
• •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of receipt of study treatment, and for 60 days (males) or 90 days (females) from the last dose of tocilizumab and for 5 months (150 days) after the last dose of atezolizumab. Administration of atezolizumab or tocilizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• •Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration
• •Patients positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive patients must have:
• •* An undetectable viral load within 6 months of registration
• •* A stable regimen of highly active anti-retroviral therapy (HAART)
• •* No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• •* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B
• •* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid \[RNA\]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
• •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• •Availability of prior radiotherapy treatment plan details in Digital Imaging and Communications in Medicine (DICOM) format