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AzTrials

GliomasPhase 1NCT03154996

Chronic Convection Enhanced Delivery of Topotecan

A Phase 1 study testing Topotecan, Gadolinium and Synchromed II infusion pumps in people with Gliomas, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gliomas
What is being tested?
Topotecan, Gadolinium and Synchromed II infusion pumps
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
18 Jan 2018to 20 Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Irving Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: 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).

Read the 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.

Conditions
Gliomas
Being tested
Topotecan, Gadolinium, Synchromed II infusion pumps
Keywords
Gliomas, Recurrent, Chronic Convection, High Grade Gliomas
Medical subject headings
Glioma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TopotecanDrug

    Also called Hycamtin, TPT

    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)

  • GadoliniumDrug

    Also called Gado

    Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.

  • Synchromed II infusion pumpsDevice

    Implanted subcutaneously to facilitate chronic infusion.

Study groups in NCT03154996
Study groupRoleWhat they receive
Long term CED of TopotecanExperimentalAn 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.
Receives: Drug: Topotecan; Drug: Gadolinium; Device: Synchromed II infusion pumps

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose at which all patients have had no greater than grade 2 adverse reactions

    This is designed to measure the safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients.

    Measured: Up to 29 days

Secondary outcomes (3)

  1. Clinical toxicity rate

    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.

    Measured: Up to 29 days

  2. Change in radiographic tumor response

    Tumor response to TPT will be investigated by MRI scan.

    Measured: Baseline, 6 weeks post-treatment

  3. Progression free survival (PFS)

    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.

    Measured: Every 3-6 months, up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2017
  2. Study start18 Jan 2018
  3. Primary completion20 Aug 2021
  4. Study completion20 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03154996
Sponsor's protocol ID
AAAQ9520
Other IDs
5R01CA161404-02
Status last verified
Jun 2022
First submitted
14 May 2017
Last updated
22 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Spinazzi EF, Argenziano MG, Upadhyayula PS, Banu MA, Neira JA, Higgins DMO, Wu PB, Pereira B, Mahajan A, Humala N, Al-Dalahmah O, Zhao W, Save AV, Gill BJA, Boyett DM, Marie T, Furnari JL, Sudhakar TD, Stopka SA, Regan MS, Catania V, Good L, Zacharoulis S, Behl M, Petridis P, Jambawalikar S, Mintz A, Lignelli A, Agar NYR, Sims PA, Welch MR, Lassman AB, Iwamoto FM, D'Amico RS, Grinband J, Canoll P, Bruce JN. Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial. Lancet Oncol. 2022 Nov;23(11):1409-1418. doi: 10.1016/S1470-2045(22)00599-X. Epub 2022 Oct 13.

    PubMed 36243020

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Topotecan, Gadolinium and Synchromed II infusion pumps in people with Gliomas, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose at which all patients have had no greater than grade 2 adverse reactions (time frame: Up to 29 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03154996, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.

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