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

Early Phase 1WithdrawnNCT03193463

Michael Vogelbaum, MD, PhD

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Glioma

Interventions

Topotecan (<=8cc)DRUG

In predominantly enhancing mass with a volume of 8 cc or less of topotecan administered

Topotecan (>8cc)DRUG

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

Cleveland Multiport CatheterDEVICE

an investigational device, will be used to deliver the topotecan

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of intra-operative catheter related complications

Documentation of possible, probable, or definite catheter-related complications

Time frame: Up to 12 months

Number of post-operative catheter related complications

Documentation of possible, probable, or definite catheter-related complications

Time frame: Up to 12 months

Number of catheter related complications after catheter removal

Documentation of possible, probable, or definite catheter-related complications

Time frame: Up to 12 months

Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan

Time frame: Up to 12 months

Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan

Time frame: Up to 12 months

Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using volumetric magnetic resonance imaging, as determined by MRI scan

Time frame: Up to 12 months

Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan

Time frame: Up to 12 months

Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion concentration, as determined by MRI scan

Time frame: Up to 12 months

Data from ClinicalTrials.gov

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes