Ensayos clínicos

Inclusion Criteria:

• 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).
• 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.
• Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression.
• Physiologic Status/Age: Patients must be 19 years of age or older (the age of consent in Nebraska).
• Patients must have recovered from any toxicity of prior therapy that in the opinion of the investigator could impact tolerance to the study drug.
• ECOG Performance Status of 0-3.
• Patients must have an adequate bone marrow reserve (ANC count ≥1,500/mm^3 , hemoglobin > 8 g/dL, platelet count ≥ 100,000/mm^3 ).
• Patients must have adequate renal and hepatic function with: a. creatinine < 1.5 x institutional upper limit of normal (ULN). b. total bilirubin < 1.5 x ULN (unless due to Gilbert's disease) c. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN d.serum alkaline phosphatase less than 2.5 times the upper limits of normal).
• 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.
• 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.
• 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).

Exclusion Criteria:

• 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.
• 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).
• Lactating or pregnant.
• History of uncontrollable allergic reactions to bevacizumab.
• 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.
• 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.
• Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to registration.
• 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.

Eligibility last updated 9/21/22. Questions regarding updates should be directed to the study team contact.