Topotecan in Glioma Undergoing A Clinically-Indicated Surgical Resection

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.