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

NCT ID: NCT03193463

Last Updated: 2019-03-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-03
• Study Completion Date: 2018-11-19

Brief 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.

Detailed 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.

Conditions

Glioma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Predominantly enhancing mass with volume of 8 cc or less

Only 1 Cleveland Multiport Catheter (CMC) will be placed and CED will be performed intra-operatively only in a magnetic resonance imaging (MRI) equipped Operating Room. Topotecan infusion will be performed over a 4-hour period, with the goal of complete tumor coverage. The initial rate will be 1.20 ml/hour 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 1.20 ml/hour based upon the tumor coverage and safety characteristics of the previously treated patients.

Group Type: EXPERIMENTAL

Topotecan (<=8cc)

Intervention Type: DRUG

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

Cleveland Multiport Catheter

Intervention Type: DEVICE

an investigational device, will be used to deliver the topotecan

Magnetic Resonance Imaging (MRI)

Intervention Type: DIAGNOSTIC_TEST

to monitor the infusion of topotecan into the tumor

Predominantly enhancing mass with volume of > 8 cc

2 Cleveland Multiport Catheter (CMCs) will be placed and the total infusion rate of Topotecan per CMC to be used for the first 24 hours for the first patient will be 0.834 ml/hour (3.48 microliters/minute/microcatheter). The rate used for the second 24 hours of the infusion will be 1.668 ml/hour. If the first patient does not experience rate-limiting toxicity, then the patient #2's initial infusion rate will start at the highest tolerated rate for patient #1, and the second 24-hour rate for that patient will be increased by 0.834 ml/hour. Each subsequent patient will undergo rate escalation in a similar manner until we observe either: 1) complete coverage of the enhancing tumor by the infused Gadopentetic acid (Gd-DTPA), or 2) rate-limiting toxicity.

Group Type: EXPERIMENTAL

Topotecan (>8cc)

Intervention Type: 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 Catheter

Intervention Type: DEVICE

an investigational device, will be used to deliver the topotecan

Magnetic Resonance Imaging (MRI)

Intervention Type: DIAGNOSTIC_TEST

to monitor the infusion of topotecan into the tumor

Predominantly non-enhancing mass

The total infusion rate of Topotecan per Cleveland Multiport Catheter (CMC) to be used for the first 24 hours for the first patient will be 0.29 ml/hour. The rate used for the second 24 hours of the infusion will be 0.58 ml/hour. If the first patient does not experience rate-limiting toxicity, then the patient #2's initial infusion rate will start at the highest tolerated rate for patient #1, and the second 24-hour rate for that patient will be increased by 0.29 ml/hour. Each subsequent patient will undergo rate escalation in a similar manner until we observe either: 1) complete coverage of the non-enhancing tumor by the infused Gd-DTPA, or 2) rate-limiting toxicity.

Group Type: EXPERIMENTAL

Cleveland Multiport Catheter

Intervention Type: DEVICE

an investigational device, will be used to deliver the topotecan

Magnetic Resonance Imaging (MRI)

Intervention Type: DIAGNOSTIC_TEST

to monitor the infusion of topotecan into the tumor

Lower Does Topotecan

Intervention Type: DRUG

Rate for non-enhancing tumors has an initial dose of 0.29ml/hour

Interventions

Topotecan (<=8cc)

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Cleveland Multiport Catheter

an investigational device, will be used to deliver the topotecan

Intervention Type: DEVICE

Magnetic Resonance Imaging (MRI)

to monitor the infusion of topotecan into the tumor

Intervention Type: DIAGNOSTIC_TEST

Lower Does Topotecan

Rate for non-enhancing tumors has an initial dose of 0.29ml/hour

Intervention Type: DRUG

Other Intervention Names

Hycamtin; Hycamtin; Hycamtin

Eligibility 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Infuseon Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

Michael Vogelbaum, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Michael Vogelbaum, MD, PhD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael A. Vogelbaum, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Other Identifiers

INFT1317

Identifier Type: -

Identifier Source: org_study_id