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

Primary Purpose

Glioma

Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Topotecan (<=8cc)
Topotecan (>8cc)
Cleveland Multiport Catheter
Magnetic Resonance Imaging (MRI)
Lower Does Topotecan
Sponsored by
Michael Vogelbaum, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma focused on measuring Topotecan, Convection-Enhanced Delivery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Predominantly enhancing mass with volume of 8 cc or less

    Predominantly enhancing mass with volume of > 8 cc

    Predominantly non-enhancing mass

    Arm Description

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Number of intra-operative catheter related complications
    Documentation of possible, probable, or definite catheter-related complications
    Number of post-operative catheter related complications
    Documentation of possible, probable, or definite catheter-related complications
    Number of catheter related complications after catheter removal
    Documentation of possible, probable, or definite catheter-related complications
    Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan
    Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan
    Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using volumetric magnetic resonance imaging, as determined by MRI scan
    Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan
    Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion concentration, as determined by MRI scan
    Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion duration, as determined by MRI scan

    Secondary Outcome Measures

    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)
    Safety as measured by the common terminology criteria for adverse events (CTCAE)
    Safety will be determined through adverse events by arm

    Full Information

    First Posted
    June 13, 2017
    Last Updated
    February 28, 2019
    Sponsor
    Michael Vogelbaum, MD, PhD
    Collaborators
    Infuseon Therapeutics, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03193463
    Brief Title
    Intratumorally-Administered Topotecan Using CED in High Grade Glioma Undergoing Stereotactic Biopsy
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    PI left institution
    Study Start Date
    November 3, 2017 (Actual)
    Primary Completion Date
    November 19, 2018 (Actual)
    Study Completion Date
    November 19, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Michael Vogelbaum, MD, PhD
    Collaborators
    Infuseon Therapeutics, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Glioma
    Keywords
    Topotecan, Convection-Enhanced Delivery

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    Model Description
    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
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Predominantly enhancing mass with volume of 8 cc or less
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Predominantly enhancing mass with volume of > 8 cc
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Predominantly non-enhancing mass
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Topotecan (<=8cc)
    Other Intervention Name(s)
    Hycamtin
    Intervention Description
    In predominantly enhancing mass with a volume of 8 cc or less of topotecan administered
    Intervention Type
    Drug
    Intervention Name(s)
    Topotecan (>8cc)
    Other Intervention Name(s)
    Hycamtin
    Intervention Description
    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
    Device
    Intervention Name(s)
    Cleveland Multiport Catheter
    Intervention Description
    an investigational device, will be used to deliver the topotecan
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    Magnetic Resonance Imaging (MRI)
    Intervention Description
    to monitor the infusion of topotecan into the tumor
    Intervention Type
    Drug
    Intervention Name(s)
    Lower Does Topotecan
    Other Intervention Name(s)
    Hycamtin
    Intervention Description
    Rate for non-enhancing tumors has an initial dose of 0.29ml/hour
    Primary Outcome Measure Information:
    Title
    Number of intra-operative catheter related complications
    Description
    Documentation of possible, probable, or definite catheter-related complications
    Time Frame
    Up to 12 months
    Title
    Number of post-operative catheter related complications
    Description
    Documentation of possible, probable, or definite catheter-related complications
    Time Frame
    Up to 12 months
    Title
    Number of catheter related complications after catheter removal
    Description
    Documentation of possible, probable, or definite catheter-related complications
    Time Frame
    Up to 12 months
    Title
    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
    Title
    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
    Title
    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
    Title
    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
    Title
    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
    Title
    Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion duration, as determined by MRI scan
    Time Frame
    Up to 12 months
    Secondary Outcome Measure Information:
    Title
    Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria
    Description
    Response includes objective response rate (ORR), median progression-free survival (PFS), proportion progression-free at six months (PFS-6), and median overall survival (OS)
    Time Frame
    Up to 12 months
    Title
    Safety as measured by the common terminology criteria for adverse events (CTCAE)
    Description
    Safety will be determined through adverse events by arm
    Time Frame
    Up to 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Michael A. Vogelbaum, MD, PhD
    Organizational Affiliation
    Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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