Malignant GliomaEarly Phase 1NCT02278510
Topotecan Using Convection-Enhanced Delivery (CED) in High Grade Glioma
A Early Phase 1 study testing Topotecan, Gadolinium DTPA and Cleveland Multiport Catheter in people with Malignant Glioma and WHO Grade III or IV Recurrent Glioma, run by Michael Vogelbaum, MD, PhD at 1 site in United States.
Trial summary
Topotecan is a FDA-approved drug when given by intravenous injection, but it is not effective against brain tumors when given intravenously. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan directly into participants' brain tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, WHO Grade III or IV Recurrent Glioma
- What is being tested?
- Topotecan, Gadolinium DTPA and Cleveland Multiport Catheter
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2014to 10 Nov 2015
- Phase
- Early 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
- Histologically confirmed diagnosis of supratentorial WHO Grade III or IV (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 of less than 40cm3 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/microliter
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- Platelet count≥100,000/microliter
- Hemoglobin≥10g/dL
- Normal PT/PTT
- Estimated glomerular filtration rate (eGFR) of at least 50mL/min
Who cannot join
- 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 CSF disease
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Pilot Trial of Intraparenchymally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive WHO Grade III or IV (High Grade) Glioma Requiring Stereotactic Biopsy
Topotecan is a FDA-approved drug when given by intravenous injection, but it is not effective against brain tumors when given intravenously. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan directly into participants' brain tumors. One purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan directly into brain tumors. This study will also evaluate different doses of topotecan that can be delivered to a participant's brain tumor with use of the Cleveland Multiport Catheter, and it will also examine how their tumor responds to treatment with topotecan.
Read the detailed description
This study will look at the way topotecan is injected into participant's tumor. A small amount of contrast dye (called gadolinium DTPA) will be added to topotecan before it is injected. Pictures will be taken of the tumor with an MRI machine. This will allow the investigators to see where in the tumor the topotecan has been injected. Issues related to patient selection, coordination with other therapeutic and palliative clinical options, and patient quality of life impact will be studied. Except for the infusion of topotecan and gadolinium DTPA into the tumor, and MRI imaging of the infusion process, all procedures and treatments participants will experience during the care of their brain tumor are non-investigational; the types of medical treatments, procedures, and tests they experience will be Standard of Care for patients with brain tumors.
Primary Objectives:
- To investigate by MR imaging the spatial and temporal distribution of topotecan in tumor and tumor-infiltrated brain 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 recurrent/progressive HGG
- To evaluate the spatial and temporal distribution of topotecan, by MR imaging, when delivered into enhancing tumor tissue versus non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium)
Secondary Objectives:
- To investigate the extent to which backflow may be observed on MRI during CED-mediated 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
- Being tested
- Topotecan, Gadolinium DTPA, Cleveland Multiport Catheter
- Keywords
- topotecan, convection-enhanced delivery, CED, High Grade Glioma
- Medical subject headings
- Glioma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
Topotecan is a chemotherapy that is approved by the FDA to treat cancers. It is normally given by an intravenous injection, and not directly into a tumor. That is why it is considered to be an investigational drug for this study
Gadolinium DTPADrug
Gadolinium DTPA is a contrast agent which will be added to topotecan to allow the investigators to observe where topotecan goes in tumors. Gadolinium DTPA is approved by the FDA for intravenous injection during an MRI scan. It is not approved by the FDA for administration directly into a tumor.
Cleveland Multiport CatheterDevice
The Cleveland Multiport Catheter is a device that is not approved by the FDA and so it is classified as an investigational device. It has been designed to deliver drugs and other agents intended to treat cancers directly into the affected tissues. The Cleveland Multiport Catheter can be placed into a brain tumor only in the operating room. It is placed during an operation to perform a biopsy of brain tumors. Following the biopsy, a surgeon will place two catheters into the tumor with use of an image guided navigation system. Once each catheter has been placed, it will be secured into the scalp and the incision will be closed. The Cleveland Multiport Catheter will be left in place until the completion of the topotecan treatment.
| Study group | Role | What they receive |
|---|---|---|
| Direct infusion of topotecan | Experimental | The experimental Cleveland Multiport Catheter will be used to inject a chemotherapy, topotecan, and a contrast agent, gadolinium DTPA, into the high grade brain tumors of study participants Receives: Drug: Topotecan; Drug: Gadolinium DTPA; Device: Cleveland Multiport Catheter |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spatial distribution of topotecan
Determination of the spatial distribution of intraparenchymally-administered topotecan over time using a gadolinium-based contrast agent, volumetric magnetic resonance imaging, and three-dimensional image reconstruction
Measured: 24 weeks
Number of catheter- and/or drug-related complications
The overall number of catheter- and/or drug-related complications occurring intra-operatively, post-operatively, or following catheter removal
Measured: 24 weeks
Secondary outcomes (4)
Objective response rate of subjects given topotecan
The mean objective response rate to using the Response Assessment in Neuro-Oncology (RANO) criteria for single-agent topotecan in recurrent/progressive HGG administered via CED.
Measured: 24 weeks
Median progression-free survival of HGG subjects given topotecan
The median progression-free survival of subjects in months using the Response Assessment in Neuro-Oncology (RANO) criteria for single-agent topotecan in recurrent/progressive GBM administered via CED.
Measured: 24 weeks
Median overall survival of HGG subjects given topotecan
The median overall survival of subjects in months using the Response Assessment in Neuro-Oncology (RANO) criteria for single-agent topotecan in recurrent/progressive GBM administered via CED.
Measured: 24 weeks
Proportion of progression free HGG subjects given topotecan
The proportion of subjects without disease progression using the Response Assessment in Neuro-Oncology (RANO) criteria for single-agent topotecan in recurrent/progressive GBM administered via CED.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2014 (estimated)
- Study start9 Dec 2014
- Primary completion10 Nov 2015
- Study completion10 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant GliomaStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Vogelbaum, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Infuseon Therapeutics, Inc.
- Responsible party
- Sponsor-investigator, Michael Vogelbaum, MD, PhD, Case Comprehensive Cancer Center
- Investigators
- Michael A Vogelbaum, MD, PhD, Principal investigator, Cleveland Clinic, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02278510
- Sponsor's protocol ID
- INFT1314
- Other IDs
- NCI-2014-02248
- Status last verified
- Mar 2017
- First submitted
- 28 Oct 2014
- Last updated
- 31 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vogelbaum MA, Brewer C, Barnett GH, Mohammadi AM, Peereboom DM, Ahluwalia MS, Gao S. First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. J Neurosurg. 2018 Apr 13;130(2):476-485. doi: 10.3171/2017.10.JNS171845. Print 2019 Feb 1.
PubMed 29652233
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Intraparenchymally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive WHO Grade III or IV (High Grade) Glioma Requiring Stereotactic Biopsy
- ClinicalTrials.gov ID
- NCT02278510
- Acronym / sponsor ID
- INFT1314
- Keywords
- topotecan, convection-enhanced delivery, CED, High Grade Glioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Michael Vogelbaum, MD, PhDUniversity, hospital or other
- Collaborators
- Infuseon Therapeutics, Inc.
- Study start
- 9 Dec 2014 (actual)
- Primary completion
- 10 Nov 2015 (actual)
- Study completion
- 10 Nov 2015 (actual)
- First posted
- 30 Oct 2014 (estimated)
- 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.
Topotecan is a FDA-approved drug when given by intravenous injection, but it is not effective against brain tumors when given intravenously. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan directly into participants' brain tumors. One purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan directly into brain tumors. This study will also evaluate different doses of topotecan that can be delivered to a participant's brain tumor with use of the Cleveland Multiport Catheter, and it will also examine how their tumor responds to treatment with topotecan.
Detailed description
This study will look at the way topotecan is injected into participant's tumor. A small amount of contrast dye (called gadolinium DTPA) will be added to topotecan before it is injected. Pictures will be taken of the tumor with an MRI machine. This will allow the investigators to see where in the tumor the topotecan has been injected. Issues related to patient selection, coordination with other therapeutic and palliative clinical options, and patient quality of life impact will be studied. Except for the infusion of topotecan and gadolinium DTPA into the tumor, and MRI imaging of the infusion process, all procedures and treatments participants will experience during the care of their brain tumor are non-investigational; the types of medical treatments, procedures, and tests they experience will be Standard of Care for patients with brain tumors.
Primary Objectives:
- To investigate by MR imaging the spatial and temporal distribution of topotecan in tumor and tumor-infiltrated brain 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 recurrent/progressive HGG
- To evaluate the spatial and temporal distribution of topotecan, by MR imaging, when delivered into enhancing tumor tissue versus non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium)
Secondary Objectives:
- To investigate the extent to which backflow may be observed on MRI during CED-mediated 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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Direct infusion of topotecan | Experimental | Drug: Topotecan, Drug: Gadolinium DTPA, Device: Cleveland Multiport CatheterThe experimental Cleveland Multiport Catheter will be used to inject a chemotherapy, topotecan, and a contrast agent, gadolinium DTPA, into the high grade brain tumors of study participants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed diagnosis of supratentorial WHO Grade III or IV (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 of less than 40cm3 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
- Absolute neutrophil count (ANC)≥1,500/microliter
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| TopotecanTopotecan is a chemotherapy that is approved by the FDA to treat cancers. It is normally given by an intravenous injection, and not directly into a tumor. That is why it is considered to be an investigational drug for this study | Drug | Direct infusion of topotecan |
| Gadolinium DTPAGadolinium DTPA is a contrast agent which will be added to topotecan to allow the investigators to observe where topotecan goes in tumors. Gadolinium DTPA is approved by the FDA for intravenous injection during an MRI scan. It is not approved by the FDA for administration directly into a tumor. | Drug | Direct infusion of topotecan |
| Cleveland Multiport CatheterThe Cleveland Multiport Catheter is a device that is not approved by the FDA and so it is classified as an investigational device. It has been designed to deliver drugs and other agents intended to treat cancers directly into the affected tissues. The Cleveland Multiport Catheter can be placed into a brain tumor only in the operating room. It is placed during an operation to perform a biopsy of brain tumors. Following the biopsy, a surgeon will place two catheters into the tumor with use of an image guided navigation system. Once each catheter has been placed, it will be secured into the scalp and the incision will be closed. The Cleveland Multiport Catheter will be left in place until the completion of the topotecan treatment. | Device | Direct infusion of topotecan |
Primary outcome
Spatial distribution of topotecan
Time frame: 24 weeks
Determination of the spatial distribution of intraparenchymally-administered topotecan over time using a gadolinium-based contrast agent, volumetric magnetic resonance imaging, and three-dimensional image reconstruction
Number of catheter- and/or drug-related complications
Time frame: 24 weeks
The overall number of catheter- and/or drug-related complications occurring intra-operatively, post-operatively, or following catheter removal
4 secondary outcomes
Objective response rate of subjects given topotecan
Time frame: 24 weeks
Median progression-free survival of HGG subjects given topotecan
Time frame: 24 weeks
Median overall survival of HGG subjects given topotecan
Time frame: 24 weeks
Proportion of progression free HGG subjects given topotecan
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2017.
- Derived from this study: PubMed 29652233Vogelbaum MA, Brewer C, Barnett GH, Mohammadi AM, Peereboom DM, Ahluwalia MS, Gao S. First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. J Neurosurg. 2018 Apr 13;130(2):476-485. doi: 10.3171/2017.10.JNS171845. Print 2019 Feb 1.
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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. This study is not recruiting at the moment.
Michael A Vogelbaum, MD, PhD principal investigator
Cleveland Clinic, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Topotecan, Gadolinium DTPA and Cleveland Multiport Catheter in people with Malignant Glioma and WHO Grade III or IV Recurrent Glioma, run by Michael Vogelbaum, MD, PhD 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 13 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 31 Mar 2017. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Spatial distribution of topotecan (time frame: 24 weeks). 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 NCT02278510, 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 31 Mar 2017; AzTrials last refreshed its copy on 7 Nov 2026.