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

• ClinicalTrials.gov Identifier: NCT03927274
• Recruitment Status: Recruiting
• Last Update Posted: September 9, 2019
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Glioma of Brain	Drug: Topotecan	Early Phase 1

Study Design

• Study Type: Interventional
• Estimated Enrollment: 5 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 23, 2019
• Estimated Primary Completion Date: April 23, 2021
• Estimated Study Completion Date: April 23, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Distribution of topotecan in tumor tissue [ Time Frame: Treatment day 1 ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Contacts

Contact: Jerry Owens; 813-745-1656; Jerry.Owens@Moffitt.org

Locations

United States, Florida

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

Contact: Jerry Owens 813-745-1656 Jerry.Owens@Moffitt.org

Contact Jerry.Owens@Moffitt.org

Principal Investigator: Michael Vogelbaum, MD, PhD

Sub-Investigator: Peter Forsyth, M.D.

Sub-Investigator: James Liu, M.D.

Sub-Investigator: Sepideh Mokhtari, M.D

Sub-Investigator: Edwin Peguero, M.D

Sub-Investigator: Solmaz Sahebjam, M.D

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Michael Vogelbaum, M.D, PhD; Moffitt Cancer Center

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials Website 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT03927274 History of Changes
• Other Study ID Numbers: MCC-19970
• First Posted: April 25, 2019
• Last Update Posted: September 9, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Glioma; Brain Tumor; High Grade Glioma

Additional relevant MeSH terms:

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Glioma; Topotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents