Brain NeoplasmPhase 1NCT00880061
An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-grade Glioma
A Phase 1 study testing IL13-PE38QQR in people with Brain Neoplasm and Glioma, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Diffusely infiltrating pontine glioma (DIPG) or supratentorial high-grade glioma (HGG) are brain tumors that are often difficult to treat. It is very difficult to get chemotherapy agents to tumors in the brain, and researchers are looking for new methods to directly treat these types of cancer. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Brain Neoplasm, Glioma
- What is being tested?
- IL13-PE38QQR
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2009to 5 Jun 2015
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age less than 18 years
- Diagnosis: recurrent or progressive:
- DIPG
- HGG
- Patients undergoing surgical resection must have measurable/evaluable disease prior to study entry.
- Histopathologic Diagnosis
Show all 20Show fewer
- A histopathologic diagnosis is not required for patients with DIPG but a biopsy may be recommended if the patient has an atypical presentation or atypical findings on MR-imaging.
- Histopathologic confirmation for patients with HGG is required. If necrosis is suspected based on MR-imaging and Nuclear Medicine scans, biopsy or surgical resection for confirmation of disease progression may be required.
- Prior Therapy
- Patients must have received at least standard doses of radiation (i.e., greater than 54 Gy).
- Surgery/biopsy - Patients must be more than 2 weeks from any neurosurgical procedure and cleared by the Principal Investigator before undergoing CED.
- Radiation - Patients must be more than 4 weeks from last fraction of radiation to the target site
- Chemotherapy - Patients must not be on concurrent chemotherapy. The last dose of chemotherapy must be greater than 2 weeks prior to CED and the patient must have recovered from any toxic effects of prior therapy (to less than Grade 2 or baseline).
- Biologic therapy - Patients must be greater than 7 days from biologic therapy.
- Investigational therapy - Patients must be greater than 30 days from any investigational therapy.
- Patients must be healthy enough to tolerate surgery and general anesthesia in the opinion of the primary investigator. This includes, but is not limited to:
- Adequate baseline organ function, including an age-adjusted normal serum creatinine OR a creatinine clearance greater or equal to 60 mL/min/1.73m(2), total bilirubin less than 2 times the upper limit of normal (ULN) and direct bilirubin within normal limits. Patients with elevated SGPT (up to 5 times ULN) will be eligible if the elevation is attributed to steroid treatment.
- If neurological deficits are present, they must be stable for at least 1 week prior to registration.
- Patients must be able to undergo MR-imaging with gadolinium-based contrast administration (e.g. no ferrous-containing implants, no pacemakers, no allergy to contrast, etc).
- All patients or their legal guardians must sign a document of informed consent indicating their understanding of the investigational nature and the potential risks associated with this study. When appropriate, pediatric patients will be included in all discussions in order to obtain verbal and written assent.
Who cannot join
- Patients with an uncorrectable bleeding disorder
- Patients with multifocal or leptomeningeal disease
- Patients with signs of impending herniation or an acute intratumoral hemorrhage
- Patients on concurrent chemotherapy or biologic therapy for the treatment of their tumor
- Patients who are pregnant or breastfeeding, because of unknown effects of the study agent, the strong magnetic fields and Gadolinium containing contrast agents on the fetus; patients of child-bearing potential must be willing to practice an effective form of birth control, including abstinence, hormone therapy, intrauterine device, 2 barrier methods.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-Grade Glioma
Background:
- Diffusely infiltrating pontine glioma (DIPG) or supratentorial high-grade glioma (HGG) are brain tumors that are often difficult to treat. It is very difficult to get chemotherapy agents to tumors in the brain, and researchers are looking for new methods to directly treat these types of cancer.
- IL-13 is an immune molecule normally occurring in the body. Patients with gliomas appear to have significant amounts of the IL-13 receptors in their brain tumors. An experimental drug, IL13-PE38QQR, combines a bacteria toxin with human IL-13 to allow the toxin to enter and destroy the tumor cell. Early clinical studies suggest this treatment may prolong survival of patients with these types of brain tumors.
- A technique called convection-enhanced delivery (CED) uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. This technique can treat a tumor more directly than with traditional methods.
Read more
Objectives:
- To test the safety and feasibility of giving IL13-PE38QQR directly into regions of the brain in pediatric patients with DIPG or HGG, using CED.
- To determine the most appropriate dose of IL13-PE38QQR to treat DIPG or HGG.
- To determine the effects of this experimental therapy on the tumor.
- To evaluate the physical changes in the tumor before and after the therapy.
Eligibility:
- Patients who are less than 18 years of age and have been diagnosed with either DIPG or with supratentorial HGG that has not responded well to standard treatments.
Design:
- Patients will be admitted to the hospital and will receive a magnetic resonance imaging (MRI) scan to show the exact location of the tumor. A small plastic tube will be inserted surgically into the tumor area, and IL13-PE38QQR and a MRI contrast agent (gadolinium DTPA) will be infused into the area.
- MRI scans will monitor the process, and the tube will be removed after surgery.
- Doses will be adjusted over the course of the study.
- Patients who respond well to treatment may be eligible to receive a second infusion, no sooner than 4 weeks after the first treatment.
- Post-treatment visits:
Clinic visits 4 and 8 weeks after the treatment, and then every 8 weeks for up to 1 year.
- Physical examination with neurological testing, an MRI, and standard blood and urine tests.
Read the detailed description
Objective: The primary purpose of this study is to test the safety and feasibility of giving a new experimental agent, called IL13-PE38QQR, directly into regions of the brain in patients with diffusely infiltrating pontine glioma (DIPG) or with recurrent or progressive supratentorial high-grade glioma (HGG) using a technique called convection-enhanced delivery or CED. CED uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. At the same time, we can watch where the molecules go in the brain by attaching a tracer, gadolinium-DTPA, to the IL13-PE38QQR, which can then be seen in the brain with magnetic resonance imaging (MRI). Because we do not know the best dose to use in patients with DIPG or HGG, we will give increasing amounts of IL13-PE38QQR to small groups of patients with each type of brain tumor, known as a dose escalation study. Secondary purposes of this study include determining the effects of this experimental therapy on the tumor, and evaluating the physical changes in the tumor before and after the therapy.
Study Population: Twenty-right pediatric patients with recurrent or progressive DIPG or supratentorial HGG that have undergone standard treatment and who meet all the Inclusion and Exclusion Criteria may be enrolled. Eighteen patients will receive treatment; an additional ten patients may be screening failures or unevaluable.
Design: We propose a Phase I single institution, open label, dose escalation (doses of 0.125, 0.25 and 0.5 micrograms/ml), safety and tolerability study of IL13-PE38QQR infused via CED into patients with either DIPG (up to 9 patients) or recurrent HGG (up to 9 patients). IL13-PE38QQR will be administered to regions of tumor determined by radiographic findings. Escalating dose levels will be evaluated in the following dose cohorts (3 patients per Cohort): Cohort 1 = 0.125 micrograms/ml, Cohort 2 = 0.25 micrograms/ml and Cohort 3 = 0.5 micrograms/ml.
Outcome Measures: To assess the safety, tolerability and potential efficacy of CED of IL13-PE38QQR, we will use detailed clinical and radiographic examinations. These will be performed at baseline and on post-infusion days 1, 28 and 60. After post-infusion day 60, clinical and radiographic studies will then be performed every 8 weeks until imaging or clinical evidence of recurrence/progressive disease or new treatment is initiated.
- Conditions
- Brain Neoplasm, Glioma
- Being tested
- IL13-PE38QQR
- Keywords
- Diffuse Infiltrating Pontine Glioma, Supratentorial High Grade Glioma, Convection-Enhanced Delivery, Pediatric Brain Tumor, Brain Tumor, Glioma
- Medical subject headings
- Brain Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL13-PE38QQRDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrently with gd-DTPA, 2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs
Secondary outcomes (1)
Determine effect of IL13-PE38QQR on MRI tumor measurements, symptom improvement or worsening, changes on clinical exam, radiographic changes, steroid dosing, QOL testing and survival of pediatric patients with DIPG and recurrent HGG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2009 (estimated)
- Study start7 Apr 2009
- Primary completion5 Jun 2015
- Study completion5 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Brain NeoplasmStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John D Heiss, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00880061
- Sponsor's protocol ID
- 090117
- Other IDs
- 09-N-0117
- Status last verified
- 5 Jun 2015
- First submitted
- 10 Apr 2009
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008 Jan 15;112(2):416-32. doi: 10.1002/cncr.23169.
PubMed 18074355Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, et al. Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg. 1991 Mar;74(3):433-40. doi: 10.3171/jns.1991.74.3.0433.
PubMed 1847194Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist. 2004;9(2):197-206. doi: 10.1634/theoncologist.9-2-197.
PubMed 15047924Robison NJ, Kieran MW. Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol. 2014 Aug;119(1):7-15. doi: 10.1007/s11060-014-1448-8. Epub 2014 May 3.
PubMed 24792486Chittiboina P, Heiss JD, Warren KE, Lonser RR. Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas. J Neurosurg Pediatr. 2014 Mar;13(3):276-82. doi: 10.3171/2013.11.PEDS136. Epub 2014 Jan 10.
PubMed 24410126
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-Grade Glioma
- ClinicalTrials.gov ID
- NCT00880061
- Acronym / sponsor ID
- 090117
- Conditions
- Brain Neoplasm, Glioma
- Keywords
- Diffuse Infiltrating Pontine Glioma, Supratentorial High Grade Glioma, Convection-Enhanced Delivery, Pediatric Brain Tumor, Brain Tumor, Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 7 Apr 2009
- Primary completion
- 5 Jun 2015 (actual)
- Study completion
- 5 Jun 2015 (actual)
- First posted
- 13 Apr 2009 (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.
Background:
- Diffusely infiltrating pontine glioma (DIPG) or supratentorial high-grade glioma (HGG) are brain tumors that are often difficult to treat. It is very difficult to get chemotherapy agents to tumors in the brain, and researchers are looking for new methods to directly treat these types of cancer.
- IL-13 is an immune molecule normally occurring in the body. Patients with gliomas appear to have significant amounts of the IL-13 receptors in their brain tumors. An experimental drug, IL13-PE38QQR, combines a bacteria toxin with human IL-13 to allow the toxin to enter and destroy the tumor cell. Early clinical studies suggest this treatment may prolong survival of patients with these types of brain tumors.
- A technique called convection-enhanced delivery (CED) uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. This technique can treat a tumor more directly than with traditional methods.
Objectives:
- To test the safety and feasibility of giving IL13-PE38QQR directly into regions of the brain in pediatric patients with DIPG or HGG, using CED.
- To determine the most appropriate dose of IL13-PE38QQR to treat DIPG or HGG.
- To determine the effects of this experimental therapy on the tumor.
- To evaluate the physical changes in the tumor before and after the therapy.
Eligibility:
- Patients who are less than 18 years of age and have been diagnosed with either DIPG or with supratentorial HGG that has not responded well to standard treatments.
Design:
- Patients will be admitted to the hospital and will receive a magnetic resonance imaging (MRI) scan to show the exact location of the tumor. A small plastic tube will be inserted surgically into the tumor area, and IL13-PE38QQR and a MRI contrast agent (gadolinium DTPA) will be infused into the area.
- MRI scans will monitor the process, and the tube will be removed after surgery.
- Doses will be adjusted over the course of the study.
- Patients who respond well to treatment may be eligible to receive a second infusion, no sooner than 4 weeks after the first treatment.
- Post-treatment visits:
Clinic visits 4 and 8 weeks after the treatment, and then every 8 weeks for up to 1 year.
- Physical examination with neurological testing, an MRI, and standard blood and urine tests.
Detailed description
Objective: The primary purpose of this study is to test the safety and feasibility of giving a new experimental agent, called IL13-PE38QQR, directly into regions of the brain in patients with diffusely infiltrating pontine glioma (DIPG) or with recurrent or progressive supratentorial high-grade glioma (HGG) using a technique called convection-enhanced delivery or CED. CED uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. At the same time, we can watch where the molecules go in the brain by attaching a tracer, gadolinium-DTPA, to the IL13-PE38QQR, which can then be seen in the brain with magnetic resonance imaging (MRI). Because we do not know the best dose to use in patients with DIPG or HGG, we will give increasing amounts of IL13-PE38QQR to small groups of patients with each type of brain tumor, known as a dose escalation study. Secondary purposes of this study include determining the effects of this experimental therapy on the tumor, and evaluating the physical changes in the tumor before and after the therapy.
Study Population: Twenty-right pediatric patients with recurrent or progressive DIPG or supratentorial HGG that have undergone standard treatment and who meet all the Inclusion and Exclusion Criteria may be enrolled. Eighteen patients will receive treatment; an additional ten patients may be screening failures or unevaluable.
Design: We propose a Phase I single institution, open label, dose escalation (doses of 0.125, 0.25 and 0.5 micrograms/ml), safety and tolerability study of IL13-PE38QQR infused via CED into patients with either DIPG (up to 9 patients) or recurrent HGG (up to 9 patients). IL13-PE38QQR will be administered to regions of tumor determined by radiographic findings. Escalating dose levels will be evaluated in the following dose cohorts (3 patients per Cohort): Cohort 1 = 0.125 micrograms/ml, Cohort 2 = 0.25 micrograms/ml and Cohort 3 = 0.5 micrograms/ml.
Outcome Measures: To assess the safety, tolerability and potential efficacy of CED of IL13-PE38QQR, we will use detailed clinical and radiographic examinations. These will be performed at baseline and on post-infusion days 1, 28 and 60. After post-infusion day 60, clinical and radiographic studies will then be performed every 8 weeks until imaging or clinical evidence of recurrence/progressive disease or new treatment is initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (20 listed)
- Age less than 18 years
- Diagnosis: recurrent or progressive:
- Patients undergoing surgical resection must have measurable/evaluable disease prior to study entry.
- Histopathologic Diagnosis
- Prior Therapy
Key exclusion criteria (5 listed)
- Patients with an uncorrectable bleeding disorder
- Patients with multifocal or leptomeningeal disease
- Patients with signs of impending herniation or an acute intratumoral hemorrhage
- Patients on concurrent chemotherapy or biologic therapy for the treatment of their tumor
- Patients who are pregnant or breastfeeding, because of unknown effects of the study agent, the strong magnetic fields and Gadolinium containing contrast agents on the fetus; patients of child-bearing potential must be willing to practice an effective form of birth control, including abstinence, hormone therapy, intrauterine device, 2 barrier methods.
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 |
|---|---|---|
| IL13-PE38QQR | Drug | – |
Primary outcome
1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrently with gd-DTPA, 2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs
1 secondary outcome
Determine effect of IL13-PE38QQR on MRI tumor measurements, symptom improvement or worsening, changes on clinical exam, radiographic changes, steroid dosing, QOL testing and survival of pediatric patients with DIPG and recurrent HGG
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 18074355Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008 Jan 15;112(2):416-32. doi: 10.1002/cncr.23169.
- Background: PubMed 1847194Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, et al. Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg. 1991 Mar;74(3):433-40. doi: 10.3171/jns.1991.74.3.0433.
- Background: PubMed 15047924Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist. 2004;9(2):197-206. doi: 10.1634/theoncologist.9-2-197.
- Derived from this study: PubMed 24792486Robison NJ, Kieran MW. Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol. 2014 Aug;119(1):7-15. doi: 10.1007/s11060-014-1448-8. Epub 2014 May 3.
- Derived from this study: PubMed 24410126Chittiboina P, Heiss JD, Warren KE, Lonser RR. Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas. J Neurosurg Pediatr. 2014 Mar;13(3):276-82. doi: 10.3171/2013.11.PEDS136. Epub 2014 Jan 10.
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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.
John D Heiss, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
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 IL13-PE38QQR in people with Brain Neoplasm and Glioma, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 20 inclusion and 5 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: stopped early, as of the sponsor's last update on 5 Jul 2018. 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 was stopped early. Results are not available in the source record.
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?
1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrently with gd-DTPA, 2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs. 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 NCT00880061, which also lists 5 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 5 Jul 2018.