Brain Neoplasms, Primary MalignantPhase 1NCT00308165
Topotecan by Intracerebral Clysis for Recurrent Primary Malignant Brain Tumors
A Phase 1 study testing Convection-Enhanced Delivery and Topotecan in people with Brain Neoplasms, Primary Malignant, run by Columbia University at 1 site in United States.
Trial summary
This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Brain Neoplasms, Primary Malignant
- What is being tested?
- Convection-Enhanced Delivery and Topotecan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Jan 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with primary malignant brain tumor, or a newly diagnosed or recurrent malignant tumor of the brainstem. Patients with tumors of the brain must have been previously treated with external beam radiation. Patients with brainstem gliomas may or may not have been previously treated.
- Patients with a tumor that is stereotactically accessible (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 100 cc in total volume).
- Patients who demonstrate evidence of increasing contrast enhancement on MR or CT imaging while on stable or increasing dose of steroid.
- Patients with a Karnofsky Performance Score of greater than or equal to 60.
- Men and women of child-bearing potential must practice birth control. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of study entry.
- Patients must possess the ability to give Informed Consent. Parent or guardian may give informed consent for minors.
Show all 10Show fewer
- Patients must be willing to and medically capable of undergoing the surgical operation.
- Patients may not be receiving other investigational agents for the treatment of malignant astrocytoma.
- 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 1 year old to participate in the study.
Who cannot join
- Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease.
- Patients with tumors involving the cerebellum, or both hemispheres.
- Patients with an active infection requiring treatment or having an unexplained febrile illness.
- Patients who are known HIV positive or who are known positive for Hepatitis B or C virus
- Patients who have received any form of radiation or chemotherapy within 4 weeks of protocol enrollment.
- Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
Show all 9Show fewer
- Patients who have previously received systemic topotecan for their tumor
- Patients less than 1 year of age
- Patients who are not able to receive an MRI scan
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center Neurological Institute
New York, New York, 10032
About this study
Official title: A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors
This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.
This study will also evaluate advanced magnetic resonance (MR) imaging techniques.
The study will assess quality of life parameters throughout the follow-up period.
Read the detailed description
Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.
Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.
Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.
- Conditions
- Brain Neoplasms, Primary Malignant
- Being tested
- Convection-Enhanced Delivery, Topotecan
- Keywords
- Recurrent Primary Malignant Brain Tumors, Brain Tumors, Neoplasms, Brain, Brain Cancer, Brain cancer treatment, Topotecan
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convection-Enhanced DeliveryProcedure or surgery
Also called Intracerebral Clysis
microinfusion pumps to deliver chemotherapy directly into brain tumors
TopotecanDrug
Also called Hycamtin
chemotherapeutic drug for the treatment of brain tumors
| Study group | Role | What they receive |
|---|---|---|
| Topotecan | Experimental | Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months. Receives: Procedure: Convection-Enhanced Delivery; Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities
Measured: During treatment, up to 5 Days
Maximum Tolerated Dose (MTD)
If 2 participants within a cohort develop dose-limiting toxicity (DLT), the prior dose level is considered the maximum tolerated dose (MTD). Dose-Limiting Toxicities (DLT) will be defined as any new (or increased from baseline) treatment-related (drug and/or device) neurological deficits as exhibited on neurological examination with severity of grade 3 or higher.
Measured: During treatment, up to 5 Days
Secondary outcomes (2)
Time to Tumor Progression/Recurrence
Time to tumor progression/recurrence in weeks.
Measured: Treatment to progression, Up to 8 years
Time to Death
Time to death measured in weeks
Measured: Treatment to Time of Death, Up to 8 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2006 (estimated)
- Study startMar 2004
- Primary completionMar 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain Neoplasms, Primary MalignantStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jeffrey Bruce, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00308165
- Sponsor's protocol ID
- AAAA4229
- Other IDs
- R01CA089395
- Status last verified
- Jun 2026
- First submitted
- 27 Mar 2006
- Last updated
- 25 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Anderson RC, Kennedy B, Yanes CL, Garvin J, Needle M, Canoll P, Feldstein NA, Bruce JN. Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J Neurosurg Pediatr. 2013 Mar;11(3):289-95. doi: 10.3171/2012.10.PEDS12142. Epub 2012 Dec 14.
PubMed 23240851
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors
- ClinicalTrials.gov ID
- NCT00308165
- Acronym / sponsor ID
- AAAA4229
- Conditions
- Brain Neoplasms, Primary Malignant
- Keywords
- Recurrent Primary Malignant Brain Tumors, Brain Tumors, Neoplasms, Brain, Brain Cancer, Brain cancer treatment, Topotecan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2004 (actual)
- Primary completion
- Mar 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 29 Mar 2006 (estimated)
- Results
- Posted 27 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.
This study will also evaluate advanced magnetic resonance (MR) imaging techniques.
The study will assess quality of life parameters throughout the follow-up period.
Detailed description
Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.
Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.
Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Topotecan | Experimental | Procedure: Convection-Enhanced Delivery, Drug: TopotecanOnce a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with primary malignant brain tumor, or a newly diagnosed or recurrent malignant tumor of the brainstem. Patients with tumors of the brain must have been previously treated with external beam radiation. Patients with brainstem gliomas may or may not have been previously treated.
- Patients with a tumor that is stereotactically accessible (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 100 cc in total volume).
- Patients who demonstrate evidence of increasing contrast enhancement on MR or CT imaging while on stable or increasing dose of steroid.
- Patients with a Karnofsky Performance Score of greater than or equal to 60.
- Men and women of child-bearing potential must practice birth control. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of study entry.
Key exclusion criteria (9 listed)
- Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease.
- Patients with tumors involving the cerebellum, or both hemispheres.
- Patients with an active infection requiring treatment or having an unexplained febrile illness.
- Patients who are known HIV positive or who are known positive for Hepatitis B or C virus
- Patients who have received any form of radiation or chemotherapy within 4 weeks of protocol enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Convection-Enhanced DeliveryAlso: Intracerebral Clysismicroinfusion pumps to deliver chemotherapy directly into brain tumors | Procedure or surgery | Topotecan |
| TopotecanAlso: Hycamtinchemotherapeutic drug for the treatment of brain tumors | Drug | Topotecan |
Primary outcome
Number of Participants With Dose Limiting Toxicities
Time frame: During treatment, up to 5 Days
Maximum Tolerated Dose (MTD)
Time frame: During treatment, up to 5 Days
If 2 participants within a cohort develop dose-limiting toxicity (DLT), the prior dose level is considered the maximum tolerated dose (MTD). Dose-Limiting Toxicities (DLT) will be defined as any new (or increased from baseline) treatment-related (drug and/or device) neurological deficits as exhibited on neurological examination with severity of grade 3 or higher.
2 secondary outcomes
Time to Tumor Progression/Recurrence
Time frame: Treatment to progression, Up to 8 years
Time to Death
Time frame: Treatment to Time of Death, Up to 8 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23240851Anderson RC, Kennedy B, Yanes CL, Garvin J, Needle M, Canoll P, Feldstein NA, Bruce JN. Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J Neurosurg Pediatr. 2013 Mar;11(3):289-95. doi: 10.3171/2012.10.PEDS12142. Epub 2012 Dec 14.
- Individual participant dataSharing planned: Undecided
Related trials for Brain Neoplasms, Primary Malignant
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
Active, not recruitingPhase 1
Determining the Biodistribution of an Imaging Tracer (68Ga-FAPi-46) in Patients With Solid Tumors or Hematologic Cancers
Anal Carcinoma, Bladder Carcinoma
Active, not recruitingPhase 1
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma
Not yet recruitingObservational study
Neurocognitive Integrity After Proton Therapy for Brain Tumor
Central Nervous System Tumour
RecruitingObservational study
Patient Perceptions Around Quality of Care Through Telemedicine in Neuro-Oncology
Central Nervous System Neoplasm, Leptomeningeal Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Bruce, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Convection-Enhanced Delivery and Topotecan in people with Brain Neoplasms, Primary Malignant, 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 10 inclusion and 9 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 25 Jun 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?
Yes. Results are posted in the registry (first posted 27 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Dose Limiting Toxicities (time frame: During treatment, up to 5 Days). The study lists 2 primary outcomes in all. 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 NCT00308165, 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 25 Jun 2026.