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

NCT03193463 | Withdrawn Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: INFT1317
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Glioma

Keywords

Topotecan; Convection-Enhanced Delivery

Outcome Measures

Primary Outcomes (9)

• Number of intra-operative catheter related complications

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

  Up to 12 months

• Number of post-operative catheter related complications

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

  Up to 12 months

• Number of catheter related complications after catheter removal

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

  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

  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

  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

  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

  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

  Up to 12 months

• 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 Outcomes (2)

• Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria

  Up to 12 months

• Safety as measured by the common terminology criteria for adverse events (CTCAE)

  Up to 12 months

Study Arms (3)

Predominantly enhancing mass with volume of 8 cc or less

EXPERIMENTAL

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.

Drug: Topotecan (<=8cc); Device: Cleveland Multiport Catheter; Diagnostic Test: Magnetic Resonance Imaging (MRI)

Predominantly enhancing mass with volume of > 8 cc

EXPERIMENTAL

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.

Drug: Topotecan (>8cc); Device: Cleveland Multiport Catheter; Diagnostic Test: Magnetic Resonance Imaging (MRI)

Predominantly non-enhancing mass

EXPERIMENTAL

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.

Device: Cleveland Multiport Catheter; Diagnostic Test: Magnetic Resonance Imaging (MRI); Drug: Lower Does Topotecan

Interventions

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

Also known as: Hycamtin

Predominantly enhancing mass with volume of > 8 cc

Cleveland Multiport Catheter DEVICE

an investigational device, will be used to deliver the topotecan

Predominantly enhancing mass with volume of 8 cc or less; Predominantly enhancing mass with volume of > 8 cc; Predominantly non-enhancing mass

Magnetic Resonance Imaging (MRI) DIAGNOSTIC_TEST

to monitor the infusion of topotecan into the tumor

Predominantly enhancing mass with volume of 8 cc or less; Predominantly enhancing mass with volume of > 8 cc; Predominantly non-enhancing mass

Lower Does Topotecan DRUG

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

Also known as: Hycamtin

Predominantly non-enhancing mass

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 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

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 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

Sponsors & Collaborators

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

MeSH Terms

Conditions

Glioma

Interventions

Topotecan; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Michael A. Vogelbaum, MD, PhD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: There will be 3 arms to this study, and they will accrue independently of each other as they reflect distinctly separable populations of patients with rHGG. Arm 1: Predominantly enhancing mass with volume of 8 cc or less. Arm 2: Predominantly enhancing mass with volume of \> 8 cc Arm 3: Predominantly non-enhancing mass

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 20, 2017
• Study Start: November 3, 2017
• Primary Completion: November 19, 2018
• Study Completion: November 19, 2018
• Last Updated: March 1, 2019

Record last verified: 2019-02