Chronic CED of TPT for Recurrent Malignant Glioma

Inclusion Criteria: 1. Patients must have recurrent malignant glioma with a history of WHO grade 3-4 IDH-mutant status and evidence of radiographic progression and suspicion of histopathological recurrence. Stereotactic biopsies will be performed to assess the presence of active tumor by frozen section prior to initiating treatment. Patients with a history of WHO grade 2 recurrent glioma, IDH-Mutant, who now demonstrate high-grade features of IDH-mutant WHO grade 3-4 will also be included. 2. Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible. 3. An MRI scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be less than 32 cc in total volume as assessed by the principal investigator based on pre-enrollment MRI. The lesion must be stereotactically accessible. 4. Karnofsky performance score must be greater than or equal to 70. 5. Men and women of childbearing potential must practice birth control. Women of childbearing potential must have a urine pregnancy test within 7 days of study entry. In accordance with topotecan administration guidelines, women must practice birth control for at least 1 month following chemotherapy infusion. Men must practice birth control for at least four months following termination of chemotherapy infusion. 6. Patients or appropriate legally authorized representatives must possess the ability to give Informed Consent. 7. Patients must be willing to and medically capable of undergoing the surgical operation. 8. Patients must be at least 18 years old. 9. Patients must not have known abnormal organ and marrow function as defined below 14 days or fewer from registration: * Leukocytes: ≥3,000/mcL * Absolute neutrophil count : ≥1,500/mcL * Platelets: ≥100,000/mcL * Total bilirubin: within normal institutional limits * AST(SGOT)/ALT(SGPT): ≤2.5 × institutional upper limit of normal * Creatinine: within normal institutional limits OR * Creatinine clearance: ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Exclusion Criteria: 1. Patients with diffuse subependymal or CSF disease. 2. Patients with tumors involving the cerebellum or both cerebral hemispheres. 3. Patients with an active infection requiring treatment or having an unexplained febrile illness. 4. Patients who are known HIV, Hepatitis B or Hepatitis C positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Topotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. HIV, Hepatitis B and Hepatitis C testing is not required for patients not known to have these infections. 5. Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk. 6. Patients who have previously received systemic topotecan for their tumor. 7. Patients who are not able to receive MRI or PET scans. 8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds. 9. Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 (CYP) 3A4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong CYP2C8 inhibitors. Patients who are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates are also ineligible. Caution should be used in patients taking other CYP2C8 - or CYP3A4/5-interacting agents as they may increase the serum concentrations of topotecan. If previously on such agents, the patient must discontinue them for at least two weeks prior to study treatment. 10. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing active infection, systemic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Women of childbearing potential who fail to demonstrate a negative pregnancy test 7 or fewer days from registration. 12. Women who are breast-feeding.