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Topotecan is an FDA-approved drug when given by intravenous infection. The purpose of this study is to determine if treatment with topotecan by an alternative method, direct delivery into the part of the brain where the tumor has spread, is safe and well tolerated. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan into tumor-infiltrated brain. A second purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan into tumor-infiltrated brain. This study will also examine how tumors responds to treatment with topotecan. This study will also look at the way topotecan is injected into tumors-infiltrated brain. A small amount of contrast dye (called gadolinium DTPA) will be added to topotecan before it is injected. Pictures will be taken of the brain with an MRI machine. This will allow the investigators to see where in the tumor-infiltrated brain the topotecan has been injected. This study will collect medical information before, during, and after treatment in order to better understand hot to make this type of procedure accessible to patients.

Primary Objectives

• To investigate by magnetic resonance (MR) imaging the spatial and temporal distribution of topotecan in tumor-infiltrated brain administered by convection-enhanced delivery (CED) in patients with recurrent/progressive WHO grade III or IV (high grade) glioma (HGG) who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy, following a clinically-indicated resection of the contrast enhancing tumor mass.
• To investigate by MR imaging the influence of catheter positioning, on the spatial and temporal distribution of topotecan administered by CED in patients with recurrent/progressive HGG
• To evaluate the extent of spatial distribution of topotecan, by MR imaging, when delivered into non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium) in the intraoperative setting, the immediate peri-operative setting, and in the post-operative setting.

Secondary Objectives

• To investigate the extent to which CED-mediated delivery of topotecan
• To investigate the extent to which infusate can be distributed in the 2 cm margin around the resection cavity by administration by CED
• To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different infusion rates.
• To observe evidence of activity of single-agent topotecan administered by CED to patients with recurrent/progressive HGG who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy.

Inclusion Criteria:

• Histologically confirmed diagnosis of supratentorial WHO Grade III or IV Glioma (High Grade Glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and surgical resection of the enhancing tumor is clinically indicated.

• Karnofsky Performance Status 70-100;

• MRI demonstration of an enhancing mass of more than 1 cm^3 and less than 100 cm^3;

• Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent; and

• Laboratory values within the following ranges:

  • Absolute neutrophil count (ANC) ≥ 1,500 / μL;
  • Platelet count ≥ 100,000 / μL;
  • Hemoglobin ≥ 10 g / dL;
  • Estimated glomerular filtration rate (eGFR) of at least 50 mL/min

Exclusion Criteria:

• Patient is mentally or legally incapacitated at the time of the study;
• Known HIV(+) or has been diagnosed with AIDS;
• Participation in another investigational drug study in the prior 4 weeks;
• Positive pregnancy test in a female;
• Patient, in the opinion of the investigator, is likely to be poorly compliant.
• Diffuse subependymal or CSF disease;
• Tumors involving the cerebellum
• Active infection requiring treatment;
• Unexplained febrile illness;
• Radiation or chemotherapy within 4 weeks of enrollment
• Systemic diseases associated with unacceptable anesthesia or operative risk;
• Personal or family history of bleeding diathesis and a coagulation profile that would preclude patient from undergoing a neurosurgical procedure
• Subject must take anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery
• Inability to undergo magnetic resonance imaging.