Topotecan in Glioma Undergoing A Clinically-Indicated Surgical Resection
Topotecan in Glioma Undergoing A Clinically-Indicated Surgical Resection
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.