Atezolizumab and Cabozantinib for the Treatment of Recurrent Glioblastoma

Eligibility Criteria

• * Signed informed consent form (ICF)
• * Ability and willingness to comply with the requirements of the study protocol
• * Age \>= 18 years
• * Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma). Archival tissue will be required for diagnosis confirmation. Receipt of archival tissue is not required for the start of treatment
• * Patients must have been previously treated with radiation and temozolomide
• * Patients must be at least 12 weeks out from completion of concurrent chemoradiation
• * Have a performance status of \>= 60 on the Karnofsky performance status (KPS)
• * Patients at either first or second recurrence will be considered eligible
• * A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to study enrollment
• * Absolute neutrophil count (ANC) \>= 1,500 /mcL
• * Platelets \>= 100,000 /mcL
• * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
• * Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• * Creatinine clearance should be calculated per institutional standard
• * Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol) OR 24 hour (h) urine protein =\< 1g
• * Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X ULN
• * Serum albumin \>= 2.8 g/dl
• * International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =\< 1.3 X ULN
• * All screening labs should be performed within 14 days (+3 working days) of treatment initiation
• * Female subject of childbearing potential should have a negative serum pregnancy test within 14 days (+/- 3 working days) of study enrollment
• * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the duration of the study and 5 months after the last dose of study treatment. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• * Male subjects should agree to use an adequate method of contraception during the course of the study and 5 months after the last dose of study treatment
• * Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel wafers will be excluded. Active treatment with the Optune device will be excluded
• * Has received radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment
• * Has clinically relevant ongoing complications from prior radiation therapy
• * Is currently participating in any other recurrent therapeutic trial after completion of chemoradiation
• * Has history of cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
• * Any serious medical condition that interferes with adherence to study procedures
• * Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
• * Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multifocal disease. Subject has multifocal glioblastoma (GBM), defined as discrete sites of contrast enhancing disease without contiguous T2/fluid attenuated inversion recovery (FLAIR) abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted
• * Has history of interstitial lung disease or active, non-infectious pneumonitis
• * Has an active infection requiring systemic therapy
• * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit
• * Contraindication for undergoing MRIs
• * Inability to comply with study and follow-up procedures
• * History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• * Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
• * Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
• * Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• * Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• * Rash must cover less than 10% of body surface area (BSA)
• * Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
• * No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• * Has a medical history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active pneumonitis
• * History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• * History of human immunodeficiency virus (HIV) infection or active hepatitis B (HBV) (chronic or acute) or hepatitis C infection
• * Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible. Patients will be sampled for HBV DNA and will be referred to a virologist to monitor for HBV re-activation
• * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• * Active tuberculosis
• * Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• * Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
• * Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1
• * Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• * Anticipation of need for a major surgical procedure (e.g., laparoscopic nephrectomy, gastrointestinal \[GI\] surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment, or of need for a minor surgery within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• * Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study
• * Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to cycle 1, day 1 or at any time during the study and for 5 months after last dose of atezolizumab
• * Patients may not receive concomitant chemotherapy, hormonal therapy, immunotherapy, or radiotherapy while patients are on study
• * MEDICATION-RELATED