HIF-2 Alpha Inhibitor PT2385 in Treating Patients With Recurrent Glioblastoma

Inclusion Criteria

• • Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria with:
• New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids
• Increase by >= 25% in the sum of the products of perpendicular diameters between the postradiotherapy scan with the smallest tumor measurement and a scan at least 12 weeks from completion of radiation therapy (RT) + temozolomide (TMZ), on stable or increasing doses of corticosteroids

** Note: clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence

• Tumor O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction, (MSPCR), or quantitative polymerase chain reaction (PCR)) are acceptable
• Patients must have a tumor tissue form indicating availability of archived tissue from a previous surgery for glioblastoma, completed and signed by a pathologist
• Patients must have measurable (defined by at least 1 cm x 1 cm) contrast-enhancing disease by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment
• Patients must be able to undergo MRI of the brain with gadolinium; patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
• Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• 12 weeks from the completion of radiation
• 6 weeks from a nitrosourea chemotherapy
• 3 weeks from a non-nitrosourea chemotherapy
• 4 weeks from any investigational (not Food and Drug Administration (FDA)-approved) agents
• 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
• Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• Absolute neutrophil count >= 1,500/microliter (mcL)
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Total bilirubin = = 60 ml/min/1.73m^2 for patients with creatinine levels above institutional normal
• Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) = = five years
• Patients must be able to swallow tablets

Exclusion Criteria

• • Patients receiving any other investigational agents are ineligible
• Patients must not have received prior anti- Vascular endothelial growth factor (VEGF) therapy including bevacizumab (i.e. patients must be bevacizumab naive)
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PT2385 are ineligible
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of PT2385
• Patients with a history of bleeding diathesis are ineligible
• Patients who have not recovered to < Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are ineligible
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/socia