Topotecan Using Convection-Enhanced Delivery (CED) in High Grade Glioma

NCT02278510 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: INFT1314NCI-2014-02248
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Topotecan is a FDA-approved drug when given by intravenous injection, but it is not effective against brain tumors when given intravenously. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan directly into participants' brain tumors. One purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan directly into brain tumors. This study will also evaluate different doses of topotecan that can be delivered to a participant's brain tumor with use of the Cleveland Multiport Catheter, and it will also examine how their tumor responds to treatment with topotecan.

Conditions

Malignant Glioma; WHO Grade III or IV Recurrent Glioma

Keywords

topotecan; convection-enhanced delivery; CED; High Grade Glioma

Outcome Measures

Primary Outcomes (2)

• Spatial distribution of topotecan

  Determination of the spatial distribution of intraparenchymally-administered topotecan over time using a gadolinium-based contrast agent, volumetric magnetic resonance imaging, and three-dimensional image reconstruction

  24 weeks

• Number of catheter- and/or drug-related complications

  The overall number of catheter- and/or drug-related complications occurring intra-operatively, post-operatively, or following catheter removal

  24 weeks

Secondary Outcomes (4)

• Objective response rate of subjects given topotecan

  24 weeks

• Median progression-free survival of HGG subjects given topotecan

  24 weeks

• Median overall survival of HGG subjects given topotecan

  24 weeks

• Proportion of progression free HGG subjects given topotecan

  24 weeks

Study Arms (1)

Direct infusion of topotecan

EXPERIMENTAL

The experimental Cleveland Multiport Catheter will be used to inject a chemotherapy, topotecan, and a contrast agent, gadolinium DTPA, into the high grade brain tumors of study participants

Drug: Topotecan; Drug: Gadolinium DTPA; Device: Cleveland Multiport Catheter

Interventions

Topotecan DRUG

Topotecan is a chemotherapy that is approved by the FDA to treat cancers. It is normally given by an intravenous injection, and not directly into a tumor. That is why it is considered to be an investigational drug for this study

Direct infusion of topotecan

Gadolinium DTPA DRUG

Gadolinium DTPA is a contrast agent which will be added to topotecan to allow the investigators to observe where topotecan goes in tumors. Gadolinium DTPA is approved by the FDA for intravenous injection during an MRI scan. It is not approved by the FDA for administration directly into a tumor.

Direct infusion of topotecan

Cleveland Multiport Catheter DEVICE

The Cleveland Multiport Catheter is a device that is not approved by the FDA and so it is classified as an investigational device. It has been designed to deliver drugs and other agents intended to treat cancers directly into the affected tissues. The Cleveland Multiport Catheter can be placed into a brain tumor only in the operating room. It is placed during an operation to perform a biopsy of brain tumors. Following the biopsy, a surgeon will place two catheters into the tumor with use of an image guided navigation system. Once each catheter has been placed, it will be secured into the scalp and the incision will be closed. The Cleveland Multiport Catheter will be left in place until the completion of the topotecan treatment.

Direct infusion of topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of supratentorial WHO Grade III or IV (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
• Karnofsky Performance Status 70-100
• MRI demonstration of a stereotactically accessible enhancing mass of less than 40cm3 that does not require resection to relieve clinically significant mass effect
• Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent
• Laboratory values within the following ranges:
• Absolute neutrophil count (ANC)≥1,500/microliter
• Platelet count≥100,000/microliter
• Hemoglobin≥10g/dL
• Normal PT/PTT
• Estimated glomerular filtration rate (eGFR) of at least 50mL/min

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Michael Vogelbaum, MD, PhD: lead
• Infuseon Therapeutics, Inc.: collaborator

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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 13;130(2):476-485. doi: 10.3171/2017.10.JNS171845. Print 2019 Feb 1.

  PMID: 29652233 DERIVED

MeSH Terms

Conditions

Glioma; Lymphoma, Follicular

Interventions

Topotecan; Gadolinium DTPA

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Pentetic Acid; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Coordination Complexes

Study Officials

• Michael A Vogelbaum, MD, PhD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: October 30, 2014
• Study Start: December 9, 2014
• Primary Completion: November 10, 2015
• Study Completion: November 10, 2015
• Last Updated: March 31, 2017

Record last verified: 2017-03

Locations

US (1)