Malignant GliomaPhase 1/2NCT00041587
Pre-operative IL13-PE38QQR in Patients With Recurrent or Progressive Malignant Glioma
A Phase 1/2 study testing IL13-PE38QQR, targeted fusion protein therapy and surgery in people with Malignant Glioma and Glioblastoma Multiforme, run by INSYS Therapeutics Inc at 6 sites in 3 countries.
Trial summary
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL13-PE38QQR is a protein that exhibits cell killing activity against a variety of IL13 receptor-positive tumor cell lines indicating that it may show a therapeutic benefit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma
- What is being tested?
- IL13-PE38QQR, targeted fusion protein therapy and surgery
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Jul 2002to Jul 2007
- Phase
- Phase 1/2
- 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
-Disease Characteristics-
Must have prior histologic diagnosis of supratentorial malignant glioma (Grade 3 or 4), including glioblastoma multiforme, anaplastic astrocytoma, or malignant mixed oligoastrocytoma (excludes glioma of unknown grade or pure oligodendroglioma). Patients with clinical/radiographic diagnosis of malignant glioma may be registered pending histologic confirmation.
Must have undergone prior surgical resection and received external beam radiotherapy with at least 48 Gy tumor dose, completed at least 8 weeks prior to study.
Must have recurrent or progressive supratentorial tumor compared with a previous study. Baseline tumor measurements must be determined within 2 weeks prior to study. Stereotaxic biopsy at study entry must confirm the presence of glioma (malignant, unless previously known). Recurrent or progressive tumor must have a solid enhancing region at least 1.0 cm and not more than 6.0 cm in maximum diameter. (One satellite lesion is permitted, if separated by 3 cm or less from the primary mass.)
-Patient Characteristics-
Age 18 or greater.
Karnofsky Performance Score must be at least 70.
Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 9 gm/dL; Platelets at least 75,000/mm^3; PT \& PTT within institutional limit of normal.
Must be candidate for re-operation.
Must have recovered from toxicity of prior therapy: at least 6 months after approved intratumoral chemotherapy (e.g. carmustine wafer); at least 6 weeks after nitrosourea-containing chemotherapy; at least 4 weeks after any investigational agent or any other cytotoxic chemotherapy; at least 2 weeks after vincristine or non-cytotoxic chemotherapy.
Must practice an effective method of birth control during the study.
Must understand the investigational nature of this study and its potential risks and benefits, and sign an approved written informed consent prior to treatment.
No patients with tumor crossing the midline (tumor involving corpus callosum is permitted if not crossing midline), more than two foci of tumor, or non-parenchymal tumor dissemination (e.g. subependymal or leptomeningeal).
No patients with impending herniation (e.g. midline shift >1 cm), spinal cord compression, uncontrolled seizures or requirement for immediate palliative treatment.
No patients who have received localized therapy for glioma, e.g. focal single-fraction radiotherapy, brachytherapy, or intracerebral infusional chemotherapy.
No patients who are receiving any concurrent chemotherapy or any other investigational agent (corticiosteroids are permitted).
Female patients must not be pregnant or breast-feeding.
No patients unwilling or unable to follow protocol requirements.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States2 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Colorado Health Sciences Center
Denver, Colorado, 80262
Germany2 sites
University Hospital Eppendorf
Hamburg, 20246
University Hospital Kiel, Department of Neurosurgery
Kiel, 24106
Israel2 sites
Sourasky Medical Center
Tel Aviv, 64239
Chaim Sheba Medical Center
Tel HaShomer, 52620
About this study
Official title: Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma: A Phase I/II Study
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL13-PE38QQR is a protein that exhibits cell killing activity against a variety of IL13 receptor-positive tumor cell lines indicating that it may show a therapeutic benefit. In reciprocal competition experiments, the interaction between IL13-PE38QQR and the IL13 receptors was shown to be highly specific for human glioma cells.
Prior to treatment, patients will have physical and neurologic exams, MRI to measure the extent of tumor, tumor biopsy, and screening laboratory tests. On Day 1, one or two catheters will be inserted directly into the tumor, after which a CT scan will be used to confirm placement. Each patient will receive one IL13-PE38QQR infusion, and the tumor will be surgically removed on approximately Day 15. In the first group of patients, IL13-PE38QQR will be infused directly into the tumor for 4 days. Depending on effectiveness or side effects of the study drug, the duration will be increased stepwise to a maximum of 7 days in subsequent groups of patients. Once duration of infusion has been determined, the dose of IL13-PE38QQR will be increased stepwise (in separate groups of patients), depending on effectiveness or side effects of the study drug. The activity of the drug against the tumor cells will be judged by examining the removed tumor tissue. Patients will have neurologic exams and MRI scans immediately after the resection and every eight weeks until disease progression is observed.
Read the detailed description
OBJECTIVES:
- To determine the maximum-tolerated dose (MTD) of IL13-PE38QQR delivered by continuous infusion via 1 or 2 intratumoral catheters into recurrent or progressive malignant glioma.
II. To determine: the pathologic effect of intratumoral IL13-PE38QQR infusion determined at Day 15 resection; the neuroradiographic characteristics of convection-enhanced drug delivery; serum levels of study drug and detect the appearance of antibody to study drug.
III. To determine the proportion of patients surviving at 6 months after continuous intratumoral IL13-PE38QQR infusion at the MTD, followed by Day 15 resection, of recurrent or progressive malignant glioma.
IV. To determine: the proportion of patients remaining disease free at 6 months; the time to progression and overall survival of patients with recurrent or progressive malignant glioma after infusion of IL13-PE38QQR at the selected dose followed by resection; the pathologic response rate of recurrent or progressive malignant glioma to IL13-PE38QQR delivered by continuous intratumoral infusion at the MTD; any additional toxicities of IL13-PE38QQR administered by stereotaxic catheters into recurrent or progressive malignant glioma at the MTD; the neuroradiographic characteristics of convection-enhanced drug delivery; serum levels of study drug and detect the appearance of antibody to study drug.
PROTOCOL OUTLINE: Patients with recurrent or progressive supratentorial malignant glioma who are considered appropriate for re-operation will be eligible for either phase of the study. Each patient will have tumor biopsy at study entry, followed by continuous intratumoral infusion of IL13-PE38QQR via 1 or 2 intratumoral catheters, placed within the enhancing portion of the tumor. Infusion rate will be held constant at 540 mL/hr (total). Toxicity will be assessed by clinical neurologic examination and laboratory values. Resection will be performed on Day 15 (6-13 days after end of infusion). Pathologic evidence of tumor necrosis will be assessed. Follow-up assessments will include neurologic examinations and MRI scans. No other anti-tumor treatment will be administered for at least 60 days after resection (except for progressive disease). Patients will be observed until death.
Phase I: The infusion duration will be escalated first in cohorts of 3-6 patients from 51.8 mL (4 days) to a maximum of 90.7 mL (7 days), to identify a MTD based on infusion duration.
Once duration is determined, IL13-PE38QQR concentration will be escalated in cohorts of 3-6 patients from 90.7 mg to a maximum of 362.8 mg (assuming 7-day infusion) to identify a MTD based on concentration.
Phase II: Patients will be treated at a selected dose no higher than the MTD to estimate the proportion of patients surviving at 6 months, time to progression and survival, and pathologic response rate.
PROJECTED ACCRUAL: In Phase I, 12-48 patients, up to 6 centers in Europe, Israel and North America. In Phase II, up to 35 efficacy evaluable patients, up to 6 centers.
- Being tested
- IL13-PE38QQR, targeted fusion protein therapy, surgery
- Keywords
- Cancer, Recurrent resectable supratentorial malignant glioma
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL13-PE38QQRDrug
targeted fusion protein therapyProcedure or surgery
surgeryProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2002 (estimated)
- Study startJul 2002
- Primary completionJun 2006
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants
Sponsor and investigators
- Lead sponsor
- INSYS Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00041587
- Sponsor's protocol ID
- IL13PEI-103
- Status last verified
- Jun 2011
- First submitted
- 10 Jul 2002
- Last updated
- 6 Jun 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma: A Phase I/II Study
- ClinicalTrials.gov ID
- NCT00041587
- Acronym / sponsor ID
- IL13PEI-103
- Keywords
- Cancer, Recurrent resectable supratentorial malignant glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants
- Lead sponsor
- INSYS Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- Jul 2002
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 12 Jul 2002 (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.
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL13-PE38QQR is a protein that exhibits cell killing activity against a variety of IL13 receptor-positive tumor cell lines indicating that it may show a therapeutic benefit. In reciprocal competition experiments, the interaction between IL13-PE38QQR and the IL13 receptors was shown to be highly specific for human glioma cells.
Prior to treatment, patients will have physical and neurologic exams, MRI to measure the extent of tumor, tumor biopsy, and screening laboratory tests. On Day 1, one or two catheters will be inserted directly into the tumor, after which a CT scan will be used to confirm placement. Each patient will receive one IL13-PE38QQR infusion, and the tumor will be surgically removed on approximately Day 15. In the first group of patients, IL13-PE38QQR will be infused directly into the tumor for 4 days. Depending on effectiveness or side effects of the study drug, the duration will be increased stepwise to a maximum of 7 days in subsequent groups of patients. Once duration of infusion has been determined, the dose of IL13-PE38QQR will be increased stepwise (in separate groups of patients), depending on effectiveness or side effects of the study drug. The activity of the drug against the tumor cells will be judged by examining the removed tumor tissue. Patients will have neurologic exams and MRI scans immediately after the resection and every eight weeks until disease progression is observed.
Detailed description
OBJECTIVES:
- To determine the maximum-tolerated dose (MTD) of IL13-PE38QQR delivered by continuous infusion via 1 or 2 intratumoral catheters into recurrent or progressive malignant glioma.
II. To determine: the pathologic effect of intratumoral IL13-PE38QQR infusion determined at Day 15 resection; the neuroradiographic characteristics of convection-enhanced drug delivery; serum levels of study drug and detect the appearance of antibody to study drug.
III. To determine the proportion of patients surviving at 6 months after continuous intratumoral IL13-PE38QQR infusion at the MTD, followed by Day 15 resection, of recurrent or progressive malignant glioma.
IV. To determine: the proportion of patients remaining disease free at 6 months; the time to progression and overall survival of patients with recurrent or progressive malignant glioma after infusion of IL13-PE38QQR at the selected dose followed by resection; the pathologic response rate of recurrent or progressive malignant glioma to IL13-PE38QQR delivered by continuous intratumoral infusion at the MTD; any additional toxicities of IL13-PE38QQR administered by stereotaxic catheters into recurrent or progressive malignant glioma at the MTD; the neuroradiographic characteristics of convection-enhanced drug delivery; serum levels of study drug and detect the appearance of antibody to study drug.
PROTOCOL OUTLINE: Patients with recurrent or progressive supratentorial malignant glioma who are considered appropriate for re-operation will be eligible for either phase of the study. Each patient will have tumor biopsy at study entry, followed by continuous intratumoral infusion of IL13-PE38QQR via 1 or 2 intratumoral catheters, placed within the enhancing portion of the tumor. Infusion rate will be held constant at 540 mL/hr (total). Toxicity will be assessed by clinical neurologic examination and laboratory values. Resection will be performed on Day 15 (6-13 days after end of infusion). Pathologic evidence of tumor necrosis will be assessed. Follow-up assessments will include neurologic examinations and MRI scans. No other anti-tumor treatment will be administered for at least 60 days after resection (except for progressive disease). Patients will be observed until death.
Phase I: The infusion duration will be escalated first in cohorts of 3-6 patients from 51.8 mL (4 days) to a maximum of 90.7 mL (7 days), to identify a MTD based on infusion duration.
Once duration is determined, IL13-PE38QQR concentration will be escalated in cohorts of 3-6 patients from 90.7 mg to a maximum of 362.8 mg (assuming 7-day infusion) to identify a MTD based on concentration.
Phase II: Patients will be treated at a selected dose no higher than the MTD to estimate the proportion of patients surviving at 6 months, time to progression and survival, and pathologic response rate.
PROJECTED ACCRUAL: In Phase I, 12-48 patients, up to 6 centers in Europe, Israel and North America. In Phase II, up to 35 efficacy evaluable patients, up to 6 centers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 | – |
| targeted fusion protein therapy | Procedure or surgery | – |
| surgery | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
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 6 Jun 2011.
Related trials for Malignant Glioma
RecruitingPhase 1
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
RecruitingEarly Phase 1
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Diffuse Glioma, Malignant Glioma
Active, not recruitingPhase 1
Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
Recurrent Glioblastoma, Recurrent Malignant Glioma
Active, not recruitingPhase 1/2
A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
Malignant Glioma
RecruitingPhase 2
Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
High Grade Glioma, CNS Tumor
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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IL13-PE38QQR, targeted fusion protein therapy and surgery in people with Malignant Glioma and Glioblastoma Multiforme, run by INSYS Therapeutics Inc at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 6 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Germany, Israel. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
Where can I read the original study information?
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 6 Jun 2011.