This early phase I trial studies topotecan hydrochloride delivered directly to the brain using convection-enhanced delivery in treating patients with high-grade glioma that has come back (recurrent) or that is growing, spreading, or getting worse (progressed) undergoing surgery. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving topotecan hydrochloride directly into the brain via a catheter that bypasses the blood brain barrier may kill more tumor cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02500459.
PRIMARY OBJECTIVES:
I. To investigate by magnetic resonance (MR) imaging the spatial and temporal distribution of topotecan (topotecan hydrochloride) in tumor-infiltrated brain administered by convection-enhanced delivery (CED) in patients with recurrent/progressive World Health Organization (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.
II. 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.
III. 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 [gadopentetate dimeglumine]) in the intraoperative setting, the immediate peri-operative setting, and in the post-operative setting.
SECONDARY OBJECTIVES:
I. To investigate the extent to which CED-mediated delivery of topotecan.
II. To investigate the extent to which infusate can be distributed in the 2 cm margin around the resection cavity by administration by CED.
III. To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different infusion rates.
IV. 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.
OUTLINE:
Patients receive topotecan hydrochloride intraparenchymally along with gadopentetate dimeglumine using a CED catheter over 24 to 72 hours. Patients undergo MRI at baseline and every 24 hours until topotecan hydrochloride administration is complete.
After completion of study treatment, patients are followed up periodically.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorMichael A. Vogelbaum
