Pulse Reduced Dose-Rate Radiation Therapy and Bevacizumab in Treating Patients with Recurrent Glioblastoma or Anaplastic Glioma Previously Treated with Radiation Therapy, Temozolomide, and/or Bevacizumab

Inclusion Criteria

• Patients must have histologically or molecularly confirmed Grade 3 or Grade 4 glioma, IDH mutant or wildtype, as defined by the 2021 World Health Organization (WHO) guidelines
• Patients must have measurable or non-measurable (evaluable) disease recurrence * Recurrence must be documented based on a combination of clinical and imaging parameters, consistent with routine clinical practice, with or without histologic confirmation * Patients may have had any number of relapses and be eligible for the study
• Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naive – groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed – groups 2 and 4); therapy with these agents may be given together or sequentially in the past
• All patients may have had prior surgery, chemotherapy, and radiation therapy; patients with prior vascular endothelial growth factor (VEGF) inhibitor exposure will be placed in the bevacizumab exposed group (groups 2 and 4); prior treatment with Gliadel is permitted for all groups
• Prior radiation requirements * For bevacizumab-naive patients (groups 1 and 3) a minimum of 6 months must have elapsed since completion of initial radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy * For bevacizumab-exposed patients (groups 2 and 4) minimum of 3 months must have elapsed since completion of initial radiation therapy and there is no minimum time since completion of last chemotherapy
• Patients must be 18 years or older
• Patients must have a KPS performance status of >= 60
• Hemoglobin >= 10 (within 14 days prior to registration)
• Platelets >= 100,000/mm^3 (within 14 days prior to registration)
• Absolute neutrophil count >= 1500/mm^3 (within 14 days prior to registration)
• Urine protein via dipstick =< 2+ or =< 100 mg/dl
• Patients’ baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to registration (systolic =< 140 mmHg, diastolic =< 90 mmHg)
• Patients must have a baseline evaluation including history and physical examination with neurological evaluation and magnetic resonance imaging (MRI) of the brain (with and without gadolinium-based contrast), all completed within 30 days prior to registration
• Females of child-bearing potential, based on institutional guidelines, must have a negative pregnancy test within 14 days prior to registration
• Females of child-bearing potential and, sexually-active males must consent to follow acceptable birth control methods to avoid conception while on treatment
• All subjects must have given signed, informed consent prior to registration on study
• Patients previously treated outside of the University of Wisconsin (UW) must have their pathology slides sent to the UW for review and confirmation * NOTE: a copy of the pathology report is sufficient for registration

Exclusion Criteria

• Patients who are pregnant or breast-feeding will NOT be eligible for participation
• Patients may NOT be on full dose anti-coagulation therapy; maintenance doses of low molecular weight heparin is permissible
• Patients with a prior malignancy will NOT be eligible for participation aside from the following exception: * Patients who have had any curatively treated invasive malignancy and have been disease free without treatment for 1 year prior to study entry ARE eligible for participation
• Patients with an active second malignancy (other than non-melanoma skin cancer or cervical cancer in situ) are NOT eligible for participation
• Patients with uncontrolled hypertension (> 140/90 mmHg) are NOT eligible for participation
• Patients who exhibit any other serious concurrent active infection or other medical illness which would jeopardize their ability to receive the therapy outlined in this protocol with reasonable safety will NOT be eligible for participation