Brain Tumor, RecurrentPhase 1TPT CED rHGGNCT06666712
Chronic CED of TPT for Recurrent Malignant Glioma
A Phase 1 study testing Topotecan in people with Brain Tumor, Recurrent and Malignant Glioma (WHO Grade III or IV), run by Jeffrey N. Bruce at 1 site in United States.
Trial summary
The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumor, Recurrent, Malignant Glioma (WHO Grade III or IV), IDH1/IDH2 Mutation
- What is being tested?
- Topotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2026to Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 recurrent malignant glioma with a history of WHO grade 3-4 IDH-mutant status and evidence of radiographic progression and suspicion of histopathological recurrence. Stereotactic biopsies will be performed to assess the presence of active tumor by frozen section prior to initiating treatment. Patients with a history of WHO grade 2 recurrent glioma, IDH-Mutant, who now demonstrate high-grade features of IDH-mutant WHO grade 3-4 will also be included.
- Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible.
- An MRI 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 as assessed by the principal investigator based on pre-enrollment MRI. The lesion must be stereotactically accessible.
- Karnofsky performance score must be greater than or equal to 70.
- Men and women of childbearing potential must practice birth control. Women of childbearing potential must have a urine pregnancy test within 7 days of study entry. In accordance with topotecan administration guidelines, women must practice birth control for at least 1 month following chemotherapy infusion. Men must practice birth control for at least four months following termination of chemotherapy infusion.
- Patients or appropriate legally authorized representatives must possess the ability to give Informed Consent.
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- Patients must be willing to and medically capable of undergoing the surgical operation.
- Patients must be at least 18 years old.
- Patients must not have known abnormal organ and marrow function as defined below 14 days or fewer from registration:
- Leukocytes: ≥3,000/mcL
- Absolute neutrophil count : ≥1,500/mcL
- Platelets: ≥100,000/mcL
- Total bilirubin: within normal institutional limits
- AST(SGOT)/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 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. HIV, Hepatitis B and Hepatitis C testing is not required for patients not known to have these infections.
- Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
- Patients who have previously received systemic topotecan for their tumor.
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- Patients who are not able to receive MRI or PET scans.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds.
- Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 (CYP) 3A4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong CYP2C8 inhibitors. Patients who are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates are also ineligible. Caution should be used in patients taking other CYP2C8 - or CYP3A4/5-interacting agents as they may increase the serum concentrations of topotecan. If previously on such agents, the patient must discontinue them for at least two weeks prior to study treatment.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing active infection, systemic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women of childbearing potential who fail to demonstrate a negative pregnancy test 7 or fewer days from registration.
- Women who are breast-feeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University Irving Medical Center / NewYork-Presbyterian Hospital
New York, New York, 10032
Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Nadine Khoury, nmk2156@cumc.columbia.edu
About this study
Official title: Chronic Convection Enhanced Delivery of Topotecan for Recurrent Malignant Glioma
The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). The secondary goal of the study is to study drug distribution and assess the tumor response to prolonged continuous CED of Topotecan.
Convection Enhanced Delivery is a novel method of drug delivery that allows administration of a drug directly to the brain. In CED, a drug pump is placed under the skin in the chest or abdominal region. The pump is connected to a catheter that is tunneled underneath the skin to the brain. The tip of the catheter then infuses Topotecan directly onto the brain tumor. There will be a total of four treatment infusions over the course of 23-29 days, with a 5-7-day rest period between each infusion. Throughout this period, patients' health will be monitored through imaging, blood draws, and regular exams. At the end of the treatment period, the pump will be removed, followed by resection of the tumor. Patients will be followed for the duration of their lives.
This is the investigator's second clinical trial studying CED of TPT in recurrent glioma. In the prior Phase 1b trial, chronic pulsatile CED safely and effectively delivered Topotecan to patients with IDH mutant recurrent Glioblastoma (WHO grade 4).
Read the detailed description
Malignant gliomas are among the most pernicious of human tumors. They are locally invasive and universally recurrent, often recurring within two centimeters of the original resection cavity. Although numerous chemotherapeutic drugs demonstrate significant anti-tumor activity in preclinical studies, their efficacy in clinical trials has been dismal; 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) can circumvent this challenge by delivering therapeutics directly to the brain, bypassing systemic circulation and the blood-brain barrier. CED uses a subcutaneously implanted catheter-pump system, enabling sustained, prolonged delivery while foregoing the need for an external catheter and bedside pump. In the most recent Phase Ib clinical trial, chronic pulsatile CED safely and effectively delivered Topotecan (TPT), a topoisomerase I inhibitor, to patients with recurrent Glioblastoma (WHO grade 4), Isocitrate Dehydrogenase wild type (IDH-WT). However, malignant glioma displays marked genetic and phenotypic heterogeneity not fully reflected by IDH-WT glioblastoma. In the current study, the investigators aim to further demonstrate the safety and efficacy of this drug delivery system in IDH mutated malignant glioma. The investigators hypothesize that extended chronic pulsatile local-regional delivery of TPT continues to be safe, effective, and feasible in patients with recurrent IDH mutated WHO grade 3-4 malignant glioma. This study will use the previously established method of CED through subcutaneously implanted pumps combined with non-invasive imaging to monitor drug distribution. As in the previous study, the drug's distribution will be characterized using an innovative, non-invasive methodology for measuring intracerebral distribution.
The hypothesis is that intracerebral CED can safely, effectively, and chronically administer TPT to patients with recurrent malignant glioma, including WHO grade 3-4 IDH1/2 mutated subtypes, and drug distribution can be measured non-invasively. The inclusion of IDH1/2 mutated glioma (WHO grade 3-4) marks an expansion from our prior Phase Ib trial to better reflect the heterogeneity of malignant glioma.
The chronic CED and non-invasive imaging methodology was developed in the porcine model and was subsequently shown to be safe for patients with recurrent WHO grade 4 glioma in the phase Ib clinical trial. Similar to the previous trial design, patients will undergo implantation of the CED catheters and subcutaneously implanted pumps, after which four cycles of TPT/gadolinium will be administered. Each cycle will include 48 hours of active drug infusion followed by five to seven days of drug holiday. Following the four cycles, the catheters and pumps will be removed and tumors will be resected. Tumoral and parenchymal distribution of gadolinium (measured by MRI) will be correlated with TPT levels (measured by mass spectrophotometry) in tissue samples obtained upon tumor resection. Cytotoxic response to TPT will be investigated by both MRI and direct histologic comparison between tissue samples taken at resection versus initial biopsy and MRI.
At the conclusion of these studies, the investigators expect to demonstrate the safe and successful delivery of chronic, high doses of TPT directly into patients' tumors, thereby avoiding the limitations imposed by conventional systemic delivery.
- Being tested
- Topotecan
- Keywords
- Brain Tumors, topotecan, Convection-Enhanced Delivery (CED), Glioma, IDH Mutation
- Medical subject headings
- Brain Neoplasms, Glioma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
Also called TPT, Hycamtin
Topotecan (TPT) is a chemotherapeutic agent that is a topoisomerase inhibitor. This intervention is uniquely distinguished through its administration using an externalized catheter and external microinfusion pump (Convection-Enhanced Delivery)
| Study group | Role | What they receive |
|---|---|---|
| Long-term CED of Topotecan | Experimental | Six patients will be treated with Topotecan by Convection-Enhanced Delivery. Four 48-hour Topotecan infusions will be carried out over the course of 23-29 days (with five to seven-day drug holiday after the first three infusions). Infusions will take place using Synchromed II infusion pumps with the same infusion parameters and experimental conditions used in our previous Phase I clinical trial and other short-term studies. Receives: Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, defined as dose at which all patients have had no greater than grade 2 adverse reactions
The primary outcome of the study is to measure the safety of prolonged CED of Topotecan in patients with recurrent IDH-mutant malignant glioma. Safety is defined as the dose at which all patients have had no greater than grade 2 adverse reactions possibly, probably, or definitely related to CED of Topotecan as measured through physical and neurologic examination, laboratory studies, radiographic studies, and adverse effects, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 out from Grade 1 (mild symptoms) to Grade 5 (death related to adverse event).
Measured: Up to 29 days
Secondary outcomes (3)
Progression Free Survival (PFS), Overall Survival (OS)
Progression Free Survival is defined as the duration of time from start of Topotecan treatment to time of progression or death from any cause, whichever occurs first. Overall survival is defined as the duration of time from the start of Topotecan treatment to death from any cause. Patients will be contacted every 3-6 months, up to 5 years, by phone until death.
Measured: Up to 5 years
Tumor Response to Treatment
The response of the tumor to TPT treatment will be measured radiographically with MRI periodically throughout the 23-29 day treatment period and on follow up 4-6 weeks after treatment, per the international criteria proposed by the updated Response Assessment in Neuro-oncology (RANO) guidelines.
Measured: Up to 29 days of treatment, and 4-6 weeks post treatment period
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2024
- Study start12 Jun 2026
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Brain Tumor, RecurrentStudies of the same condition, open and under way.
- 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
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jeffrey N. Bruce
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jeffrey N. Bruce, Columbia University
- Investigators
- Jeffrey Bruce, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06666712
- Sponsor's protocol ID
- AAAV1710
- Acronym
- TPT CED rHGG
- Status last verified
- Jun 2026
- First submitted
- 5 Oct 2024
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sonabend AM, Stuart RM, Yun J, Yanagihara T, Mohajed H, Dashnaw S, Bruce SS, Brown T, Romanov A, Sebastian M, Arias-Mendoza F, Bagiella E, Canoll P, Bruce JN. Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump. Neuro Oncol. 2011 Aug;13(8):886-93. doi: 10.1093/neuonc/nor051. Epub 2011 Jul 12.
PubMed 21750007Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-73. doi: 10.1056/NEJMoa0808710.
PubMed 19228619Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, Gilbert MR, Yang C. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020 May;122(11):1580-1589. doi: 10.1038/s41416-020-0814-x. Epub 2020 Apr 15.
PubMed 32291392Spinazzi 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 36243020Bruce JN, Fine RL, Canoll P, Yun J, Kennedy BC, Rosenfeld SS, Sands SA, Surapaneni K, Lai R, Yanes CL, Bagiella E, DeLaPaz RL. Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan. Neurosurgery. 2011 Dec;69(6):1272-9; discussion 1279-80. doi: 10.1227/NEU.0b013e3182233e24.
PubMed 21562434Bhowmik A, Khan R, Ghosh MK. Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int. 2015;2015:320941. doi: 10.1155/2015/320941. Epub 2015 Mar 19.
PubMed 25866775
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Convection Enhanced Delivery of Topotecan for Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT06666712
- Acronym / sponsor ID
- TPT CED rHGG / AAAV1710
- Keywords
- Brain Tumors, topotecan, Convection-Enhanced Delivery (CED), Glioma, IDH Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Jeffrey N. BruceUniversity, hospital or other
- Study start
- 12 Jun 2026 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 31 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). The secondary goal of the study is to study drug distribution and assess the tumor response to prolonged continuous CED of Topotecan.
Convection Enhanced Delivery is a novel method of drug delivery that allows administration of a drug directly to the brain. In CED, a drug pump is placed under the skin in the chest or abdominal region. The pump is connected to a catheter that is tunneled underneath the skin to the brain. The tip of the catheter then infuses Topotecan directly onto the brain tumor. There will be a total of four treatment infusions over the course of 23-29 days, with a 5-7-day rest period between each infusion. Throughout this period, patients' health will be monitored through imaging, blood draws, and regular exams. At the end of the treatment period, the pump will be removed, followed by resection of the tumor. Patients will be followed for the duration of their lives.
This is the investigator's second clinical trial studying CED of TPT in recurrent glioma. In the prior Phase 1b trial, chronic pulsatile CED safely and effectively delivered Topotecan to patients with IDH mutant recurrent Glioblastoma (WHO grade 4).
Detailed description
Malignant gliomas are among the most pernicious of human tumors. They are locally invasive and universally recurrent, often recurring within two centimeters of the original resection cavity. Although numerous chemotherapeutic drugs demonstrate significant anti-tumor activity in preclinical studies, their efficacy in clinical trials has been dismal; 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) can circumvent this challenge by delivering therapeutics directly to the brain, bypassing systemic circulation and the blood-brain barrier. CED uses a subcutaneously implanted catheter-pump system, enabling sustained, prolonged delivery while foregoing the need for an external catheter and bedside pump. In the most recent Phase Ib clinical trial, chronic pulsatile CED safely and effectively delivered Topotecan (TPT), a topoisomerase I inhibitor, to patients with recurrent Glioblastoma (WHO grade 4), Isocitrate Dehydrogenase wild type (IDH-WT). However, malignant glioma displays marked genetic and phenotypic heterogeneity not fully reflected by IDH-WT glioblastoma. In the current study, the investigators aim to further demonstrate the safety and efficacy of this drug delivery system in IDH mutated malignant glioma. The investigators hypothesize that extended chronic pulsatile local-regional delivery of TPT continues to be safe, effective, and feasible in patients with recurrent IDH mutated WHO grade 3-4 malignant glioma. This study will use the previously established method of CED through subcutaneously implanted pumps combined with non-invasive imaging to monitor drug distribution. As in the previous study, the drug's distribution will be characterized using an innovative, non-invasive methodology for measuring intracerebral distribution.
The hypothesis is that intracerebral CED can safely, effectively, and chronically administer TPT to patients with recurrent malignant glioma, including WHO grade 3-4 IDH1/2 mutated subtypes, and drug distribution can be measured non-invasively. The inclusion of IDH1/2 mutated glioma (WHO grade 3-4) marks an expansion from our prior Phase Ib trial to better reflect the heterogeneity of malignant glioma.
The chronic CED and non-invasive imaging methodology was developed in the porcine model and was subsequently shown to be safe for patients with recurrent WHO grade 4 glioma in the phase Ib clinical trial. Similar to the previous trial design, patients will undergo implantation of the CED catheters and subcutaneously implanted pumps, after which four cycles of TPT/gadolinium will be administered. Each cycle will include 48 hours of active drug infusion followed by five to seven days of drug holiday. Following the four cycles, the catheters and pumps will be removed and tumors will be resected. Tumoral and parenchymal distribution of gadolinium (measured by MRI) will be correlated with TPT levels (measured by mass spectrophotometry) in tissue samples obtained upon tumor resection. Cytotoxic response to TPT will be investigated by both MRI and direct histologic comparison between tissue samples taken at resection versus initial biopsy and MRI.
At the conclusion of these studies, the investigators expect to demonstrate the safe and successful delivery of chronic, high doses of TPT directly into patients' tumors, thereby avoiding the limitations imposed by conventional systemic delivery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Long-term CED of Topotecan | Experimental | Drug: TopotecanSix patients will be treated with Topotecan by Convection-Enhanced Delivery. Four 48-hour Topotecan infusions will be carried out over the course of 23-29 days (with five to seven-day drug holiday after the first three infusions). Infusions will take place using Synchromed II infusion pumps with the same infusion parameters and experimental conditions used in our previous Phase I clinical trial and other short-term studies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have recurrent malignant glioma with a history of WHO grade 3-4 IDH-mutant status and evidence of radiographic progression and suspicion of histopathological recurrence. Stereotactic biopsies will be performed to assess the presence of active tumor by frozen section prior to initiating treatment. Patients with a history of WHO grade 2 recurrent glioma, IDH-Mutant, who now demonstrate high-grade features of IDH-mutant WHO grade 3-4 will also be included.
- Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible.
- An MRI 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 as assessed by the principal investigator based on pre-enrollment MRI. The lesion must be stereotactically accessible.
- Karnofsky performance score must be greater than or equal to 70.
- Men and women of childbearing potential must practice birth control. Women of childbearing potential must have a urine pregnancy test within 7 days of study entry. In accordance with topotecan administration guidelines, women must practice birth control for at least 1 month following chemotherapy infusion. Men must practice birth control for at least four months following termination of chemotherapy infusion.
Key exclusion criteria (12 listed)
- Patients with diffuse subependymal or 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. HIV, Hepatitis B and Hepatitis C testing is not required for patients not known to have these infections.
- Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
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 |
|---|---|---|
| TopotecanAlso: TPT, HycamtinTopotecan (TPT) is a chemotherapeutic agent that is a topoisomerase inhibitor. This intervention is uniquely distinguished through its administration using an externalized catheter and external microinfusion pump (Convection-Enhanced Delivery) | Drug | Long-term CED of Topotecan |
Primary outcome
Safety, defined as dose at which all patients have had no greater than grade 2 adverse reactions
Time frame: Up to 29 days
The primary outcome of the study is to measure the safety of prolonged CED of Topotecan in patients with recurrent IDH-mutant malignant glioma. Safety is defined as the dose at which all patients have had no greater than grade 2 adverse reactions possibly, probably, or definitely related to CED of Topotecan as measured through physical and neurologic examination, laboratory studies, radiographic studies, and adverse effects, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 out from Grade 1 (mild symptoms) to Grade 5 (death related to adverse event).
3 secondary outcomes
Progression Free Survival (PFS), Overall Survival (OS)
Time frame: Up to 5 years
Tumor Response to Treatment
Time frame: Up to 29 days of treatment, and 4-6 weeks post treatment period
Clinical Toxicity Rate
Time frame: Up to 29 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Background: PubMed 21750007Sonabend AM, Stuart RM, Yun J, Yanagihara T, Mohajed H, Dashnaw S, Bruce SS, Brown T, Romanov A, Sebastian M, Arias-Mendoza F, Bagiella E, Canoll P, Bruce JN. Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump. Neuro Oncol. 2011 Aug;13(8):886-93. doi: 10.1093/neuonc/nor051. Epub 2011 Jul 12.
- Background: PubMed 19228619Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-73. doi: 10.1056/NEJMoa0808710.
- Background: PubMed 32291392Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, Gilbert MR, Yang C. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020 May;122(11):1580-1589. doi: 10.1038/s41416-020-0814-x. Epub 2020 Apr 15.
- Background: PubMed 36243020Spinazzi 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.
- Background: PubMed 21562434Bruce JN, Fine RL, Canoll P, Yun J, Kennedy BC, Rosenfeld SS, Sands SA, Surapaneni K, Lai R, Yanes CL, Bagiella E, DeLaPaz RL. Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan. Neurosurgery. 2011 Dec;69(6):1272-9; discussion 1279-80. doi: 10.1227/NEU.0b013e3182233e24.
- Background: PubMed 25866775Bhowmik A, Khan R, Ghosh MK. Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int. 2015;2015:320941. doi: 10.1155/2015/320941. Epub 2015 Mar 19.
- Individual participant dataSharing planned: Undecided
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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.
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 Topotecan in people with Brain Tumor, Recurrent and Malignant Glioma (WHO Grade III or IV), run by Jeffrey N. Bruce 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 16 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 15 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeffrey Bruce, MD (212-305-7346, jnb2@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, defined as 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 NCT06666712, which also lists 6 linked publications.
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 15 Jun 2026.