Treatment of Patients With Recurrent High-Grade Glioma With APG-157 and Bevacizumab

Eligibility Criteria

• 1. Patients must have pathologically proven diagnosis of high grade (aka grade III or IV) glioma that has progressed on bevacizumab (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma, H3K27M mutant glioma).
• 2. Patients must have received prior radiation therapy and standard temozolomide. Patients who have received any number of therapies for previous progressions will be considered eligible.
• 3. Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.
• 4. Physiologic Status/Age: Patients must be 19 years of age or older (the age of consent in Nebraska.)
• 5. Patients must have recovered from any toxicity of prior therapy to Grade 1 or less.
• 6. ECOG Performance Status of 0-3.
• 7. Patients must have an adequate bone marrow reserve (ANC count ≥1,500/mm3, hemoglobin \> 8 g/dL, platelet count ≥100,000/mm3).
• 8. Patients must have adequate renal and hepatic function with:
• 1. creatinine \< 1.5 x institutional upper limit of normal (ULN).
• 2. total bilirubin \< 1.5 x ULN (unless due to Gilbert's disease)
• 3. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5 x ULN
• 4. serum alkaline phosphatase less than 2.5 times the upper limits of normal)
• 9. The patient must willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.
• 10. Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment.
• 11. Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study. (Non-child bearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries).
• 1. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral APG-157, or put the study outcomes at undue risk
• 2. Immunotherapy, chemotherapy, radiotherapy, or experimental therapy within one full cycle period before first dose of study drug (i.e., for lomustine 6 weeks, for temozolomide 4 weeks)
• 3. Lactating or pregnant
• 4. History of uncontrollable allergic reactions to bevacizumab
• 5. Clinically Significant Cardiovascular Disease Defined as follows:
• * Inadequately controlled hypertension (i.e., systolic blood pressure (SBP) \> 160 mm Hg and/or diastolic blood pressure (DBP) \> 90 mm Hg despite antihypertensive therapy)
• * History of cerebrovascular accident (CVA) within 6 months
• * Myocardial infarction or unstable angina within 6 months
• 6. Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event \> Grade 3 within 4 weeks prior to registration. Note: Patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks
• 7. Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture within the last two months.
• 8. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration.
• 9. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to registration
• 10. Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent