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Vogelbaum MA, Brewer C, Barnett GH, et al. First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. J Neurosurg. 2018;1-10doi: 10.3171/2017.10.JNS171845.
Vogelbaum, M. A., Brewer, C., Barnett, G. H., Mohammadi, A. M., Peereboom, D. M., Ahluwalia, M. S., & Gao, S. (2018). First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. Journal of neurosurgery, 1-10. https://doi.org/10.3171/2017.10.JNS171845
Vogelbaum, Michael A, et al. "First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1." Journal of neurosurgery vol. (2018): 1-10. doi: https://doi.org/10.3171/2017.10.JNS171845
Vogelbaum MA, Brewer C, Barnett GH, Mohammadi AM, Peereboom DM, Ahluwalia MS, Gao S. First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. J Neurosurg. 2018 Apr 01;1-10. doi: 10.3171/2017.10.JNS171845. Epub 2018 Apr 01. PMID: 29652233.
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J Neurosurg. 2018 Apr 01;1-10. doi: 10.3171/2017.10.JNS171845. Epub 2018 Apr 01.

First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1.

Journal of neurosurgery

Michael A Vogelbaum, Cathy Brewer, Gene H Barnett, Alireza M Mohammadi, David M Peereboom, Manmeet S Ahluwalia, Shenqiang Gao

Affiliations

  1. 1Brain Tumor and Neuro-Oncology Center and.
  2. 3Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio.
  3. Departments of2Neurosurgery and.

PMID: 29652233 DOI: 10.3171/2017.10.JNS171845

Abstract

OBJECTIVEProgress in management of high-grade gliomas (HGGs) has been hampered by poor access of potential therapeutics to the CNS. The Cleveland Multiport Catheter (CMC), which deploys 4 independent delivery microcatheters, was developed to be a reliable, high-volume delivery device for delivery of therapeutic agents to the brain and other solid organs. The authors undertook this first-in-human clinical trial effort to evaluate the delivery characteristics of the CMC in patients with HGGs.METHODSA series of pilot studies were launched after approval of a sponsor-investigator IND (investigational new drug) application to evaluate the delivery of topotecan and gadolinium-DTPA (Gd-DTPA) via the CMC in patients with recurrent HGG. The first pilot trial evaluated delivery into enhancing tumor and nonenhancing, tumor-infiltrated brain. Two catheters were placed with the use of a conventional frameless stereotactic technique following a biopsy to confirm tumor recurrence, and drug infusion was performed both intraoperatively and postoperatively for a total of 96 hours with the same rate for all microcatheters. Delivery was assessed by intermittent MRI.RESULTSThree patients were enrolled in the first pilot study. MRI demonstrated delivery from all 6 catheters (24 microcatheters). The volume of distribution (Vd) of Gd-DTPA was heavily dependent upon CMC location (enhancing vs nonenhancing) with an approximately 10-fold difference in Vd observed (p = 0.005). There were no hemorrhages related to catheter placement or removal, and all 3 patients completed the protocol-defined treatment.CONCLUSIONSThe CMC is capable of providing backflow-resistant drug delivery to the brain and brain tumors. The volume of distribution is heavily dependent upon the integrity of the blood-brain barrier. Assessment of delivery is essential for development of loco-regionally applied therapeutics in the CNS.Clinical trial registration no.: NCT02278510 (clinicaltrials.gov).

Keywords: AE = adverse event; BBB = blood-brain barrier; CED = convection-enhanced delivery; CMC = Cleveland Multiport Catheter; GBM = glioblastoma; HGG = high-grade glioma; IND = investigational new drug; IRB = institutional review board; IV = intravenous; KPS = Karnofsky Performance Status; NSDU = neurological step-down unit; OR = operating room; PTFE = polytetrafluoroethylene; TMZ = temozolomide; Vd = volume of distribution; convection-enhanced delivery; glioma; oncology; surgical technique; surgical therapeutic; topotecan

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