Intratumorally-Administered Topotecan Using CED in High Grade Glioma Undergoing Stereotactic Biopsy

Glioma Clinical Trial

Official title:

Pilot Trial 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 (IND 117,240)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03193463
• Other study ID #: INFT1317
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: November 3, 2017
• Est. completion date: November 19, 2018

Study information

• Verified date: February 2019
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with topotecan by an alternative method, direct delivery into brain tumors, is safe and well tolerated. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan into your brain tumor. A second purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan into your brain tumor.

This study will also determine the best dose of topotecan to deliver to your tumor with use of the Cleveland Multiport Catheter and will also examine how your tumor responds to treatment with topotecan.

Description:

Primary Objectives

• To investigate by MR imaging the spatial and temporal distribution of topotecan in enhancing or nonenhancing bulk tumor administered by convection-enhanced delivery (CED) in patients with recurrent/progressive 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.

• To investigate by MR imaging the influence of the rate and topotecan concentration, on the spatial and temporal distribution of topotecan administered by CED in patients with with recurrent/progressive HGG

Secondary Objectives

• To investigate the extent to which backflow may be observed on MRI during CEDmediated delivery of topotecan

• To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different doses and infusion rates.

• 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 19, 2018
• Est. primary completion date: November 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Karnofsky Performance Status 70-100

• MRI demonstration of a stereotactically accessible enhancing mass 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 / µL

• Platelet count = 100,000 / µL

• Hemoglobin = 10 g / dL

• prothrombin time (PT) / partial thromboplastin time (PTT) not above institutional norms

• Estimated glomerular filtration rate (eGFR) of at least 50 mL/min

Exclusion Criteria:

• 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 cerebrospinal 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

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• Topotecan (<=8cc)
In predominantly enhancing mass with a volume of 8 cc or less of topotecan administered
• Topotecan (>8cc)
In predominantly enhancing mass with a volume of > 8 cc of topotecan administered. Initial rate is 0.834ml/hour with an increase to 1.668 ml/hour at the second infusion

Device:
• Cleveland Multiport Catheter
an investigational device, will be used to deliver the topotecan

Diagnostic Test:
• Magnetic Resonance Imaging (MRI)
to monitor the infusion of topotecan into the tumor

Drug:
• Lower Does Topotecan
Rate for non-enhancing tumors has an initial dose of 0.29ml/hour

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Michael Vogelbaum, MD, PhD	Infuseon Therapeutics, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of intra-operative catheter related complications	Documentation of possible, probable, or definite catheter-related complications	Up to 12 months
Primary	Number of post-operative catheter related complications	Documentation of possible, probable, or definite catheter-related complications	Up to 12 months
Primary	Number of catheter related complications after catheter removal	Documentation of possible, probable, or definite catheter-related complications	Up to 12 months
Primary	Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan		Up to 12 months
Primary	Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan		Up to 12 months
Primary	Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using volumetric magnetic resonance imaging, as determined by MRI scan		Up to 12 months
Primary	Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan		Up to 12 months
Primary	Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion concentration, as determined by MRI scan		Up to 12 months
Primary	Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion duration, as determined by MRI scan		Up to 12 months
Secondary	Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria	Response includes objective response rate (ORR), median progression-free survival (PFS), proportion progression-free at six months (PFS-6), and median overall survival (OS)	Up to 12 months
Secondary	Safety as measured by the common terminology criteria for adverse events (CTCAE)	Safety will be determined through adverse events by arm	Up to 12 months