Phase I/II Study to Evaluate the Safety and Clinical Efficacy of Atezolizumab (Anti-PD-L1) in Combination With Cabozantinib in Patients With Recurrent Glioblastoma (rGBM)
This phase I/II trial tests the safety and side effects of atezolizumab in combination with cabozantinib and whether they work to shrink tumors in patients with glioblastoma that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help control the disease in patients with recurrent glioblastoma.
• 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