Topotecan Using Convection-Enhanced Delivery (CED) in High Grade Glioma

This study will look at the way topotecan is injected into participant's tumor. A small
amount of contrast dye (called gadolinium DTPA) will be added to topotecan before it is
injected. Pictures will be taken of the tumor with an MRI machine. This will allow the
investigators to see where in the tumor the topotecan has been injected. Issues related to
patient selection, coordination with other therapeutic and palliative clinical options, and
patient quality of life impact will be studied. Except for the infusion of topotecan and
gadolinium DTPA into the tumor, and MRI imaging of the infusion process, all procedures and
treatments participants will experience during the care of their brain tumor are
non-investigational; the types of medical treatments, procedures, and tests they experience
will be Standard of Care for patients with brain tumors.

Primary Objectives:

- To investigate by MR imaging the spatial and temporal distribution of topotecan in
tumor and 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.

- To investigate by MR imaging the influence of the rate and topotecan concentration, on
the spatial and temporal distribution of topotecan administered by CED in patients with
recurrent/progressive HGG

- To evaluate the spatial and temporal distribution of topotecan, by MR imaging, when
delivered into enhancing tumor tissue versus non-enhancing tumor tissue (as defined on
pre-operative conventional MRI imaging with and without intravenous gadolinium)

Secondary Objectives:

- To investigate the extent to which backflow may be observed on MRI during CED-mediated
delivery of topotecan

- To assess the safety, tolerability and toxicity profile of topotecan administered by
CED using different doses and 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 (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 a sterotactic biopsy is indicated for confirmation of
recurrence/progression

- Karnofsky Performance Status 70-100

- MRI demonstration of a stereotactically accessible enhancing mass of less than 40cm3
that does not require resection to relieve clinically significant mass effect

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

Laboratory values within the following ranges:

- Absolute neutrophil count (ANC)>=1,500/microliter

- Platelet count>=100,000/microliter

- Hemoglobin>=10g/dL

- Normal PT/PTT

- Estimated glomerular filtration rate (eGFR) of at least 50mL/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 8 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

- Tumor enhancement involving both hemispheres

- Active infection requiring treatment

- Unexplained febrile illness

- Radiation or chemotherapy within 4 weeks of enrollment

- Systemic diseases associated with unacceptable anesthesia or operative risk

- Inability to undergo magnetic resonance imaging