Chronic Convection Enhanced Delivery of Topotecan for Recurrent Malignant Glioma
The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). The secondary goal of the study is to study drug distribution and assess the tumor response to prolonged continuous CED of Topotecan. Convection Enhanced Delivery is a novel method of drug delivery that allows administration of a drug directly to the brain. In CED, a drug pump is placed under the skin in the chest or abdominal region. The pump is connected to a catheter that is tunneled underneath the skin to the brain. The tip of the catheter then infuses Topotecan directly onto the brain tumor. There will be a total of four treatment infusions over the course of 23-29 days, with a 5-7-day rest period between each infusion. Throughout this period, patients' health will be monitored through imaging, blood draws, and regular exams. At the end of the treatment period, the pump will be removed, followed by resection of the tumor. Patients will be followed for the duration of their lives. This is the investigator's second clinical trial studying CED of TPT in recurrent glioma. In the prior Phase 1b trial, chronic pulsatile CED safely and effectively delivered Topotecan to patients with IDH mutant recurrent Glioblastoma (WHO grade 4).
• 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.
• Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible.
• 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.
• Karnofsky performance score must be greater than or equal to 70.
• 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.
• Patients or appropriate legally authorized representatives must possess the ability to give Informed Consent.
• Patients must be willing to and medically capable of undergoing the surgical operation.
• Patients must be at least 18 years old.
• 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.