Brain and Central Nervous System TumorsPhase 1/2NCT00053040
Immunotoxin Therapy in Treating Children With Recurrent Malignant Gliomas
A Phase 1/2 study testing cintredekin besudotox and conventional surgery in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium.
Trial summary
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- cintredekin besudotox and conventional surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2005to not given
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed grade 3 or 4 supratentorial malignant glioma by prior surgery or biopsy
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Malignant mixed oligoastrocytoma
- Recurrent or progressive disease by radiology
- In first progression or recurrence (for patients in the phase II portion of the study only)
- Must have 1 solid primary lesion with a solid component measuring at least 1 cm in diameter
- Must have received external beam radiotherapy with tumor dose of at least 48 Gy
- Planning to undergo gross total resection of the tumor to remove all contrast-enhancing components of the tumor
- No multifocal tumor not amenable to gross tumor resection
- No contrast-enhancing tumor component crossing the midline
- No subependymal or leptomeningeal tumor dissemination
- No clinically significant increased intracranial pressure (e.g., impending herniation)
- No spinal cord compression
- No requirement for immediate palliative treatment
PATIENT CHARACTERISTICS:
Age
- 3 to 21
Performance status
- Karnofsky 60-100% (over 16 years of age)
- Lansky 60-100 (16 years of age and under)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Hemoglobin at least 10 g/dL*
- Platelet count at least 100,000/mm^3* NOTE: *Transfusion independent
Hepatic
- PT and PTT normal
Renal
- Creatinine normal for age
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled seizures
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 8 weeks since prior hematopoietic stem cell transplantation
Chemotherapy
- No prior intracerebral chemotherapy for malignant glioma (except polifeprosan 20 with carmustine implant)
- At least 6 months since prior polifeprosan 20 with carmustine implant
- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
- At least 2 weeks since prior vincristine or noncytotoxic chemotherapy
- No concurrent chemotherapy
Endocrine therapy
- Concurrent steroids allowed
Radiotherapy
- See Disease Characteristics
- At least 8 weeks since prior radiotherapy
- No prior focal radiotherapy for malignant glioma (e.g., single-fraction stereotaxic radiotherapy or brachytherapy)
- Prior stereotactic radiosurgery boost as part of the initial fractionated external beam radiotherapy regimen allowed
Surgery
- See Disease Characteristics
Other
- Recovered from prior therapy
- No prior investigational intracerebral agents
- At least 4 weeks since prior systemic investigational agents
- No prior localized antitumor therapy for malignant glioma
- No concurrent anticoagulants or antiplatelet therapy, including, but not limited to, any of the following:
- Heparin
- Fractionated heparin
- Warfarin
- Aspirin
- Ticlopidine
- Clopidogrel
- Dipyridamole
- No other concurrent investigational agents
About this study
Official title: Phase I/II Trial Of Intracerebral IL13-PE38QQR Infusions In Pediatric Patients With Recurrent Malignant Glioma
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
- Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
- Estimate the rate of survival after initial progression in patients treated at the maximum safe flow rate and MTiC with this drug. (Phase II)
Secondary
- Describe the overall safety and tolerability of this regimen in these patients from the start of infusion through disease progression or initiation of alternative treatment.
- Determine the IL13 receptor α2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas
- Estimate the progression-free survival of patients treated with this drug. (Phase II)
OUTLINE: This is a multicenter, dose-escalation study.
- Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later, patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed after completion of the infusion.
Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed concentration until the maximum safe flow rate is determined. The maximum safe flow rate is defined as the rate prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.
Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive IL13-PE38QQR at escalating concentrations at the maximum safe flow rate until the maximum tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the concentration prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.
- Phase II: Patients receive IL13-PE38QQR as above at the maximum safe flow rate and MTiC determined in the phase I of the study.
Patients are followed at week 18 after catheter placement and then every 8 weeks thereafter until death, disease progression, or completion of six months (phase I) or 12 months (phase II) of follow-up after the end of IL13-PE38QQR infusion. Phase II patients who complete one year of follow-up without disease progression are followed every 12 weeks thereafter until death.
PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for phase II) will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- cintredekin besudotox, conventional surgery
- Keywords
- recurrent childhood brain tumor
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cintredekin besudotoxBiological
Also called IL13-PE38QQR
IL13-PE38QQR is administered intracerebrally by continuous convection enhanced infusion at a starting concentration of 0.25 μg/mL. Infusion duration will be held constant at 96 hours (4 days). The phase I component of this study is to estimate the maximum safe total flow rate and the maximum safe infusion concentration.
conventional surgeryProcedure or surgery
Conventional surgery is used for tumor resection prior to catheter placement for IL13-PE38QQR infusion.
| Study group | Role | What they receive |
|---|---|---|
| Surgery for tumor resection + IL13-PE38QQR infusion | Experimental | Not described Receives: Biological: cintredekin besudotox; Procedure: conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)
Toxicities reported are those occurring from the start of the IL13 infusion after catheter placement to Day 35 (30 days after the end of the infusion) if there are no or mild MRI changes on Day 35 around the catheter tract or tip. If the MRI change on Day 35 indicates moderate or extensive changes around the catheter tract or tip then the toxicities reported are those occurring from the start of the IL13 infusion to Day 75 (70 days after the end of the infusion).
Measured: Start of IL13-PE38QQR infusion to Day 35 or Day 75
Maximum safe flow rate (Phase I)
Two total flow rates of IL13-PE38QQR, 500 uL/hr and 750 uL/hr, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum safe flow rate. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Measured: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Maximum tolerated infusion concentration (Phase I)
Two infusion concentrations of IL13-PE38QQR, .25 ug/mL and .50 ug/mL, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum tolerated infusion concentration. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Measured: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Survival post initial recurrence or progression at the maximum safe total flow rate and maximum tolerated infusion concentration (Phase II)
Measured: Initial progression to date of death from any cause
Secondary outcomes (4)
Progression-free survival (Phase II)
Measured: Initial progression to second progression
IL13receptor α2 chain expression status and distribution
Expression of the IL13 receptor α2 chain will be determined by immunohistochemistry analysis of previously banked fixed primary tumor sections in addition to samples obtained during the on-study resection. Expression of the IL13 receptor α2 chain will also be determined by western blot analysis of previously banked fresh frozen primary tumor samples in addition to samples of relapsed fresh frozen tumor obtained during the on-study resection.
Measured: Pre-treatment
Overall safety
Adverse events reported are those occurring from the start of the IL13 infusion after catheter placement to the maximum of disease progression, start of alternative therapy, withdrawal from the study, death, or completion of the follow-up period. Adverse events will be tabulated by first occurrence of the event, by body system, by maximum severity, and by the highest degree of relationship to the study medication.
Measured: Start of IL13-PE38QQR infusion to disease progression or alternative treatment
Tolerability
Adverse events reported are those occurring from the start of the IL13 infusion after catheter placement to the maximum of disease progression, start of alternative therapy, withdrawal from the study, death, or completion of the follow-up period. Adverse events will be tabulated by first occurrence of the event, by body system, by maximum severity, and by the highest degree of relationship to the study medication.
Measured: Start of IL13-PE38QQR infusion to disease progression or alternative treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2003 (estimated)
- Study startOct 2005
Why it stopped: Withdrawal of pharmaceutical company support for the investigational drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Anuradha Banerjee, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00053040
- Sponsor's protocol ID
- CDR0000269073
- Other IDs
- PBTC-011C, NEOPHARM-IL13PEI-151, NCI-5930
- Status last verified
- Sep 2010
- First submitted
- 27 Jan 2003
- Last updated
- 24 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial Of Intracerebral IL13-PE38QQR Infusions In Pediatric Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00053040
- Acronym / sponsor ID
- CDR0000269073
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- recurrent childhood brain tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawal of pharmaceutical company support for the investigational drug
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2005
- First posted
- 28 Jan 2003 (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.
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.
Detailed description
OBJECTIVES:
Primary
- Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
- Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
- Estimate the rate of survival after initial progression in patients treated at the maximum safe flow rate and MTiC with this drug. (Phase II)
Secondary
- Describe the overall safety and tolerability of this regimen in these patients from the start of infusion through disease progression or initiation of alternative treatment.
- Determine the IL13 receptor α2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas
- Estimate the progression-free survival of patients treated with this drug. (Phase II)
OUTLINE: This is a multicenter, dose-escalation study.
- Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later, patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed after completion of the infusion.
Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed concentration until the maximum safe flow rate is determined. The maximum safe flow rate is defined as the rate prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.
Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive IL13-PE38QQR at escalating concentrations at the maximum safe flow rate until the maximum tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the concentration prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.
- Phase II: Patients receive IL13-PE38QQR as above at the maximum safe flow rate and MTiC determined in the phase I of the study.
Patients are followed at week 18 after catheter placement and then every 8 weeks thereafter until death, disease progression, or completion of six months (phase I) or 12 months (phase II) of follow-up after the end of IL13-PE38QQR infusion. Phase II patients who complete one year of follow-up without disease progression are followed every 12 weeks thereafter until death.
PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for phase II) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgery for tumor resection + IL13-PE38QQR infusion | Experimental | Biological: cintredekin besudotox, Procedure: conventional surgery |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| cintredekin besudotoxAlso: IL13-PE38QQRIL13-PE38QQR is administered intracerebrally by continuous convection enhanced infusion at a starting concentration of 0.25 μg/mL. Infusion duration will be held constant at 96 hours (4 days). The phase I component of this study is to estimate the maximum safe total flow rate and the maximum safe infusion concentration. | Biological | Surgery for tumor resection + IL13-PE38QQR infusion |
| conventional surgeryConventional surgery is used for tumor resection prior to catheter placement for IL13-PE38QQR infusion. | Procedure or surgery | Surgery for tumor resection + IL13-PE38QQR infusion |
Primary outcome
Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)
Time frame: Start of IL13-PE38QQR infusion to Day 35 or Day 75
Toxicities reported are those occurring from the start of the IL13 infusion after catheter placement to Day 35 (30 days after the end of the infusion) if there are no or mild MRI changes on Day 35 around the catheter tract or tip. If the MRI change on Day 35 indicates moderate or extensive changes around the catheter tract or tip then the toxicities reported are those occurring from the start of the IL13 infusion to Day 75 (70 days after the end of the infusion).
Maximum safe flow rate (Phase I)
Time frame: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Two total flow rates of IL13-PE38QQR, 500 uL/hr and 750 uL/hr, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum safe flow rate. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Maximum tolerated infusion concentration (Phase I)
Time frame: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Two infusion concentrations of IL13-PE38QQR, .25 ug/mL and .50 ug/mL, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum tolerated infusion concentration. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Survival post initial recurrence or progression at the maximum safe total flow rate and maximum tolerated infusion concentration (Phase II)
Time frame: Initial progression to date of death from any cause
4 secondary outcomes
Progression-free survival (Phase II)
Time frame: Initial progression to second progression
IL13receptor α2 chain expression status and distribution
Time frame: Pre-treatment
Overall safety
Time frame: Start of IL13-PE38QQR infusion to disease progression or alternative treatment
Tolerability
Time frame: Start of IL13-PE38QQR infusion to disease progression or alternative treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2010.
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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.
Anuradha Banerjee, MD study chair
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing cintredekin besudotox and conventional surgery in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium.
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: withdrawn, as of the sponsor's last update on 24 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I) (time frame: Start of IL13-PE38QQR infusion to Day 35 or Day 75). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
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 24 Sep 2010.