Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection

Inclusion Criteria 1. Male and female patients aged ≥ 18 years with histologically confirmed diagnosis of a stereotactically accessible, supratentorial, contrast-enhancing WHO Grade III or IV glioma (HGG) with a maximum volume between 2 and 20 cm3. • NOTE: Only patients with a histologically confirmed diagnosis of WHO Grade IV glioma (glioblastoma) meeting the above criteria will be eligible for enrollment in the first 3 dose cohorts (ie, dose concentration levels). 2. Patient must have completed standard of care chemoradiation (ie, treatment with temozolomide and radiation) and have evidence of tumor recurrence or progression based on imaging studies within the previous 21 days that supports a clinically-indicated resection. 3. Patient understands the procedures and investigational nature of the study drug and agrees to comply with study requirements by providing written informed consent. 4. Patient must have KPS ≥ 70. 5. At the time of study treatment, patients must have recovered from the toxic effects of prior therapy or meet the following criteria, or both: * More than 1 week from last noncytotoxic therapy * More than 4 weeks from last cytotoxic therapy, radiation, or treatment with bevacizumab 6. Patient must have adequate bone marrow and organ function as follows: a. Adequate bone marrow function: * Absolute neutrophil count (ANC) ≥ 1500 μL * Leukocyte count ≥ 3000 μL * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100,000 μL b. Adequate hepatic function: * Aspartate aminotransferase (AST) \< 2.5 × institutional upper limit of normal (ULN) * Alanine aminotransferase (ALT) \< 2.5 × institutional ULN * Total bilirubin ≤ 1.5 institutional ULN c. Adequate renal function: * Glomerular filtration rate (GFR) ≥ 50 mL/min by Cockcroft Gault equation d. Adequate coagulation function: * Prothrombin time (PT)/partial thromboplastin time (PTT) not above institutional norms. Note: patients receiving anticoagulant therapy are eligible for enrollment but must have values below the ULN at the time of surgery. 7. Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control) before study entry, for the duration of the study, and for a minimum of 6 months after study completion. 8. Women of child-bearing potential must have a negative beta-human chorionic gonadoptropin (hCG) serum pregnancy test within 21 days, and a negative urine pregnancy test within 24 hours, before receiving study treatment. 9. Patients must be able to undergo contrast and noncontrast MRI studies. Exclusion Criteria A patient who meets any of the following criteria will be excluded from participation in this study: 10. Patient has any significant medical illness that, in the investigator's opinion, may compromise the patient's ability to participate in the study. 11. Patient has participated in another investigational therapeutic drug study in the previous 4 weeks. 12. Patient has any of the following tumor characteristics: * Multicentric disease - defined as tumors that have multiple discrete areas of contrast enhancement separated by intervening brain and not connected by T2-weighted-Fluid- attenuated Inversion Recovery (FLAIR) abnormality * Contrast-enhancing tumor that extends into the opposite cerebral hemisphere * Nonparenchymal tumor dissemination (subependymal or leptomeningeal) * Tumor located in the posterior fossa * Significant mass effect requiring urgent resection. 13. Patient has a history of hypersensitivity reaction to gadolinium contrast agents. 14. Patient is unable to undergo MRI. 15. Patient has a known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). 16. Patient has an active infection (requiring treatment) or an unexplained febrile illness. 17. Patient is receiving anticoagulants, antiplatelets, or nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be stopped for surgery. 18. Patient is receiving escalating doses of steroids to treat mass effect. Note: patients on stable corticosteroid doses ≤ 4 mg of dexamethasone (or the equivalent of another corticosteroid) daily are eligible for the study.