Intratumorally-Administered Topotecan Using Convection-Enhanced Delivery in Patients With Grade III/ IV Glioma

A Study of Intratumorally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive World Health Organization (WHO) Grade III or IV (High Grade) Glioma Undergoing Stereotactic Biopsy

The purpose of this study is to determine if treatment with Topotecan by an alternative method, delivering topotecan directly into brain tumors, is safe and well tolerated.

Study Overview

• Status: Terminated
• Conditions: Glioma of Brain
• Intervention / Treatment: Drug: Topotecan

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sebastian Matzza; Phone Number: 813-745-1158; Email: sebastian.matzza@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• 18 years of age or older
• Karnofsky Performance Status 70-100;
• MRI demonstration of a stereotactically accessible enhancing or predominantly non- enhancing mass that does not require resection to relieve clinically significant mass effect;
• Participant understands the procedures and agrees to comply with the study requirements by providing written informed consent
• Adequate organ function as indicated in protocol

Exclusion Criteria:

• Participant 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 Cerebral Spinal 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 (MRI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cleveland Multiport Catheter (CMC) + Topotecan; For predominantly enhanced tumors with volume of 8 cc or less, only 1 Cleveland Multiport Catheter (CMC) will be placed and convection-enhanced delivery (CED) will be performed over a 4-hour period within an MRI scanner, with the goal of complete tumor coverage (as evidenced by tracer distribution on MRI). The initial rate will be 1.20 ml/hour (5.0 microliters/minute/microcatheter) and infusion will be monitored by intermittent MRI imaging. The rate may be adjusted upwards during the infusion, in the event of incomplete tumor coverage, or downwards, if new mass effect is apparent. Following completion of the 4-hour infusion, the CMC will be removed. The initial rate for each subsequent patient may be adjusted upwards in increments of up to 5 microliters/minute/microcatheter based upon the tumor coverage and safety characteristics of the previously treated patients.

Drug: Topotecan; Intratumorally-administered topotecan using convection-enhanced delivery (CED) in patients with suspected recurrent/progressive High Grade Glioma (HGG) requiring stereotactic biopsy and is focused on investigating topotecan brain tissue distribution and determining the safety, toxicity, and tolerability of intratumorally-administered topotecan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of topotecan in tumor tissue	The spatial distribution of intratumorally-administered topotecan will be determined using a gadolinium-based contrast agent, volumetric magnetic resonance imaging, and three-dimensional image reconstruction.	Treatment day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs) experienced by participants		Up to 48 weeks
Extent of topotecan backflow	Investigate the extent to which backflow may be observed on MRI during CED-mediated delivery of topotecan	Treatment day 1

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Michael Vogelbaum, M.D, PhD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): May 24, 2023
• Study Completion (Actual): May 24, 2023

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Glioma; Brain Tumor; High Grade Glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: MCC-19970

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No