Chronic Convection Enhanced Delivery of Topotecan

April 17, 2026 updated by: Columbia University

Chronic Convection Enhanced Delivery of Topotecan for Recurrent High Grade Gliomas

The primary goal of this study is to establish, for the first time, safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients with recurrent high grade glioma (HGG). Secondary objectives will include determination of topotecan (TPT) distribution and radiographic tumor response with prolonged continuous intracerebral convection-enhanced delivery (CED).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Malignant gliomas are among the most pernicious of human tumors - locally invasive and universally recurrent, with recurrence usually occurring within two centimeters of the original resection cavity. Although numerous chemotherapeutic drugs demonstrate significant anti-tumor activity in preclinical studies, the efficacy in clinical trials has been dismal because systemic delivery fails to achieve therapeutic drug levels in tumor cells due to various factors including limited blood-brain barrier permeability and systemic toxicity.

Convection-enhanced delivery (CED) is a method of regional drug delivery that circumvents this problem. Phase 1 clinical trial has shown that a potent topoisomerase inhibitor, topotecan (TPT), can be safely and effectively delivered by CED into patients with recurrent malignant gliomas. This study will expand on these clinical results to address two current limitations to the clinical application of CED: 1) A reliable method for non-invasively monitoring drug distribution throughout the tumor and brain does not exist; and 2) Duration of CED therapy has been limited to short-term infusions secondary to the use of externalized infusion pumps.

The hypothesis is that extended chronic local-regional delivery of TPT is safe, effective and feasible in patients with recurrent gliomas. TPT will be directly and chronically delivered into the tumor and surrounding brain by CED through subcutaneously implanted pumps while innovating a methodology for monitoring the drug distribution through non-invasive imaging. This strategy will overcome the limitations of chemotherapy as currently used in the treatment of gliomas, and may be applicable to other central nervous system (CNS) diseases currently limited by drug delivery barriers.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have a recurrent malignant glioma (World Health Organization (WHO) grade III-IV), including recurrent glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma. Stereotactic biopsies will be performed to confirm this diagnosis prior to initiating the treatment.
  • Patients with tumors of the brain must have been previously treated with surgical resection, external beam radiation, and temozolomide chemotherapy.
  • An magnetic resonance (MR) scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be less than 32 cc in total volume. The lesion must be stereotactically accessible.
  • Patients must have demonstrated evidence of increasing contrast enhancement on MR or computed tomography (CT) imaging while on stable or increasing dose of steroid.
  • Karnofsky performance score of greater than or equal to 60.
  • Men and women of childbearing potential must practice birth control. Women of child bearing potential must have a urine pregnancy test within 7 days of study entry.
  • Patients must possess the ability to give Informed Consent.
  • Patients must be willing to and medically capable of undergoing the surgical operation.
  • There is no upper age limit. Patients at extreme upper end of the age spectrum will not be automatically excluded, but will be carefully scrutinized to determine their suitability for this procedure.
  • Patients must be at least 18 years old.

  • Patients must have normal organ and marrow function as defined below:

    • Leukocytes: ≥3,000/ cells per microliter of blood (mcL)
    • Absolute neutrophil count: ≥1,500/mcL
    • Platelets: ≥100,000/mcL
    • Total bilirubin: within normal institutional limits
    • aspartate aminotransferase (AST) (SGOT)/alanine aminotransferase (ALT) (SGPT): ≤2.5 × institutional upper limit of normal
    • Creatinine: within normal institutional limits OR
    • Creatinine clearance: ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Exclusion Criteria:

  • Patients with diffuse subependymal or cerebral spinal fluid (CSF) disease.
  • Patients with tumors involving the cerebellum or both cerebral hemispheres.
  • Patients with an active infection requiring treatment or having an unexplained febrile illness.
  • Patients who are known HIV, Hepatitis B or Hepatitis C positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with topotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
  • Patients who have previously received systemic topotecan for their tumor
  • Patients who are not able to receive an MRI scan.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Long term CED of Topotecan
An additional 5 patients will be treated with TPT by CED maintained for 32 days. TPT infusions will be carried out for 32 days using Synchromed II infusion pumps with the same infusion parameters and experimental conditions used in the short term studies.
Drug: Topotecan

Topotecan is a chemotherapeutic agent that is a topoisomerase inhibitor. TPT is administered through an externalized catheter and external microinfusion pump.

Dose: 146 micrometers (uM)

Other Names:
  • Hycamtin
  • TPT
Drug: Gadolinium
Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.
Other Names:
  • Gado
Device: Synchromed II infusion pumps
Implanted subcutaneously to facilitate chronic infusion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose at which all patients have had no greater than grade 2 adverse reactions
Time Frame: Up to 29 days
This is designed to measure the safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients.
Up to 29 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinical toxicity rate
Time Frame: Up to 29 days
This is defined by the number of serious adverse events occuring, which is projected to be ≤ 5% at 23-29 days. A clinical toxicity rate that exceeds 20% will be considered unacceptable for this procedure.
Up to 29 days
Change in radiographic tumor response
Time Frame: Baseline, 6 weeks post-treatment
Tumor response to TPT will be investigated by MRI scan.
Baseline, 6 weeks post-treatment
Progression free survival (PFS)
Time Frame: Every 3-6 months, up to 5 years
The length of time during and after the treatment of disease that a patient lives with the disease but it does not get worse. Patients will be contacted every 3-6 months, up to 5 years, by phone until death.
Every 3-6 months, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Columbia University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeffrey Bruce, MD, jnb2@cumc.columbia.edu

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 18, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 20, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AAAQ9520
  • 5R01CA161404-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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