Intratumorally-Administered Topotecan Using CED in High Grade Glioma Undergoing Stereotactic Biopsy

Primary Objectives

- To investigate by MR imaging the spatial and temporal distribution of topotecan in
enhancing or nonenhancing bulk tumor 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
with recurrent/progressive HGG

Secondary Objectives

- To investigate the extent to which backflow may be observed on MRI during CEDmediated
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 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 a stereotactic biopsy is indicated for confirmation of
recurrence/progression

- Karnofsky Performance Status 70-100

- MRI demonstration of a stereotactically accessible enhancing mass 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 / μL

- Platelet count ≥ 100,000 / μL

- Hemoglobin ≥ 10 g / dL

- prothrombin time (PT) / partial thromboplastin time (PTT) not above institutional
norms

- 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 cerebrospinal fluid (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