Malignant GliomaPhase 1NCT00024557
Histologic Effect/Safety of Pre/Post-Operative IL13-PE38QQR in Recurrent Resectable Supratentorial Malignant Glioma Patients
A Phase 1 study testing IL13-PE38QQR, targeted fusion protein therapy and surgery in people with Malignant Glioma and Glioblastoma Multiforme, run by INSYS Therapeutics Inc at 4 sites in United States.
Trial summary
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL3-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
- 40 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2001to Jul 2007
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
-Disease Characteristics-
Must have had prior histologically-confirmed diagnosis of supratentorial malignant glioma, grade 3 or 4, either on prior pathology or on biopsy at study entry, including anaplastic astrocytoma, glioblastoma multiforme, mixed oligoastrocytoma, or malignant astrocytoma NOS.
Must have undergone prior surgical resection.
Must have received cranial radiotherapy (RT), with tumor dose of at least 48 Gy, completed at least 4 weeks prior to study entry.
Must have radiographic evidence of recurrent or progressive supratentorial tumor. If 12 weeks or less has elpased since external beam RT or localized RT (gamma-knife, brachytherapy), progression must be confirmed by metabolic imaging (MRS or PET).
Tumor sample at study entry must confirm recurrent tumor.
-Patient Characteristics-
Age 18 or greater.
Karnofsky Performance Score of at least 70.
Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 9 gm/dL; Platelets at least 100,000/mm^3.
Coagulation Status: PT \& PTT less than or equal to the upper limit of normal.
Must be candidate for re-operation.
Must have recovered from toxicity of prior therapy; at least 6 weeks elapsed since receiving nitrosourea-containing chemotherapy, at least 4 weeks since receiving other cytotoxic therapy or an investigational agent, at least 2 weeks since receiving non-cytotoxic agents or vincristine.
Must understand the investigational nature of this study and its potential risks and benefits, and sign informed consent.
Must practice an effective method of birth control.
No patients with signs of impending herniation, midline shift greater than 1 cm, uncontrolled seizures, or other neurologic conditions which would interfere with evaluation.
No patients receiving any concurrent anti-tumor therapy (other than steroids).
No patients with multifocal disease, or subependymal or leptomeningial tumor spread.
No patients with metallic prosthesis that would prevent MRI and/or MRS scanning of the brain.
Female patients must not be pregnant or breast-feeding.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Yale University
New Haven, Connecticut, 06520
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: Phase I Study to Assess the Histologic Effect and Safety of Pre-Operative and Post-Operative Infusions of IL13-PE38QQR Cytotoxin in Patients With Recurrent Resectable Supratentorial Malignant Glioma
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL3-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.
Patients will receive IL13-PE38QQR via a catheter placed directly into the brain tumor. Tumor recurrence will be confirmed by biopsy. The next day, patients will start a continuous 48-hour infusion of IL13-PE38QQR into the tumor. The dose (concentration) will be increased in the pre-resection infusion until the endpoint is reached (histologic evidence of tumor cytotoxicity or a maximum tolerated dose). Tumor resection will be planned for one week after biopsy, plus or minus 1 day. A histologically-effective concentration (HEC) will be determined using pathologic observations. At the end of resection, three catheters will be placed in brain tissue next to the resection site and assessed within 24 hours using MRI. On the second day after surgery, IL13-PE38QQR infusion will begin and will continue for 4 days. The lowest pre-resection IL13-PE38QQR concentration will be used as the starting dose for post-resection infusions. After an HEC or maximum tolerated dose (MTD) is determined, the pre-resection infusion will no longer be administered. Subsequent patients will have tumor resection and placement of three peri-tumoral catheters at study entry. IL13-PE38QQR will be infused starting on the second day after surgery and continuing for 4 days. Escalation of the post-resection IL13-PE38QQR concentration will be continued until the previously-defined HEC or MTD is reached, after which duration of the post-resection infusion will be increased in one day increments for up to 6 days. If a post-resection MTD is obtained, there will be no increase in duration of infusion. In the final stage of the study, catheters will be placed 2 days after tumor resection, and a 4-day IL13-PE38QQR infusion will begin the day after catheter placement. Patients will be observed clinically and radiographically for toxicity and duration of tumor control.
Read the detailed description
OBJECTIVES:
- Determine the concentration of IL13-PE38QQR that produces histologic evidence of toxicity to tumor, and the corresponding drug toxicity, following a 2-day continuous infusion into recurrent malignant glioma prior to surgical resection.
II. Determine the toxicity of IL13-PE38QQR administered as a 4-day continuous infusion via catheters into brain adjacent to tumor resection site, after surgical resection, at concentrations up to the selected concentration.
III. Determine the toxicity of increasing duration of continuous infusion of IL13- PE38QQR via catheters into brain adjacent to tumor resection site, after surgical resection, at the selected concentration.
IV. Determine the feasibility and safety of IL13-PE38QQR administration following post-operative placement of stereotaxic catheters 2 days after tumor resection, utilizing a post-operative imaging study for planning of catheter placement. A 4-day continuous infusion at the MTD is planned.
- Describe the time to progression and survival of patients treated with IL13-PE38QQR.
PROTOCOL OUTLINE: This study is designed to determine two dose levels. The first is defined as the histologically effective concentration (HEC) when the agent is administered prior to tumor resection. The second is defined using safety and tolerability of study drug administered after tumor resection at doses up to the HEC. Safety and tolerability of increasing duration of infusion after tumor resection will then be assessed.
Patient cohorts will be treated at escalating pre-resection dose-levels until a stopping criterion for the pre-surgery dose is met, holding the post-resection dose constant at the starting level. Stopping criteria for dose escalation of the pre-surgery infusion are determination of the HEC or the maximum tolerated dose (MTD).
Subsequent cohorts will be treated only post-operatively at escalating dose levels until a stopping criterion for the post-surgery dose is met. Stopping criteria for dose escalation of the post-surgery infusion are reaching the HEC determined for the pre-operative infusion or determination of the MTD. After the HEC is reached, subsequent cohorts will be treated with post-operative infusions of increasing duration at the HEC until the maximum duration defined in the study is reached or an MTD is defined. (If an MTD has already detected, duration will not be escalated.)
After the stage of the study evaluating escalation of infusion duration has completed, the study will expand to evaluate post-operative placement of catheters after tumor resection. This stage of the study will assess the feasibility and safety of stereotaxic placement of catheters 2 days after tumor resection using a post-operative imaging study for planning. Patients will receive a 96 hour post-resection infusion at the MTD.
Cohorts of at least three patients will be entered at each dose level. Each cohort will be observed for at least thirty days after completion of administration of study drug to allow for observation of toxicity before the next cohort is enrolled.
PROJECTED ACCRUAL: Depends on number of dose-levels, estimated at 25-50 patients.
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma, Mixed Oligoastrocytoma, Malignant Astrocytoma
- Being tested
- IL13-PE38QQR, targeted fusion protein therapy, surgery
- Keywords
- neurosurgery, craniotomy, convection-enhanced delivery, CNS interstitial infusion, recombinant toxins, malignant glioma, recurrent, intratumoral therapy, positive pressure microinfusion
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma, Recurrence
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 posted21 Sep 2001 (estimated)
- Study startJun 2001
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants
Sponsor and investigators
- Lead sponsor
- INSYS Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00024557
- Sponsor's protocol ID
- IL13PEI-002
- Status last verified
- Jun 2011
- First submitted
- 20 Sep 2001
- 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
- Phase I Study to Assess the Histologic Effect and Safety of Pre-Operative and Post-Operative Infusions of IL13-PE38QQR Cytotoxin in Patients With Recurrent Resectable Supratentorial Malignant Glioma
- ClinicalTrials.gov ID
- NCT00024557
- Acronym / sponsor ID
- IL13PEI-002
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma, Mixed Oligoastrocytoma, Malignant Astrocytoma
- Keywords
- neurosurgery, craniotomy, convection-enhanced delivery, CNS interstitial infusion, recombinant toxins, malignant glioma, recurrent, intratumoral therapy, positive pressure microinfusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- INSYS Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- Jun 2001
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 21 Sep 2001 (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). IL3-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.
Patients will receive IL13-PE38QQR via a catheter placed directly into the brain tumor. Tumor recurrence will be confirmed by biopsy. The next day, patients will start a continuous 48-hour infusion of IL13-PE38QQR into the tumor. The dose (concentration) will be increased in the pre-resection infusion until the endpoint is reached (histologic evidence of tumor cytotoxicity or a maximum tolerated dose). Tumor resection will be planned for one week after biopsy, plus or minus 1 day. A histologically-effective concentration (HEC) will be determined using pathologic observations. At the end of resection, three catheters will be placed in brain tissue next to the resection site and assessed within 24 hours using MRI. On the second day after surgery, IL13-PE38QQR infusion will begin and will continue for 4 days. The lowest pre-resection IL13-PE38QQR concentration will be used as the starting dose for post-resection infusions. After an HEC or maximum tolerated dose (MTD) is determined, the pre-resection infusion will no longer be administered. Subsequent patients will have tumor resection and placement of three peri-tumoral catheters at study entry. IL13-PE38QQR will be infused starting on the second day after surgery and continuing for 4 days. Escalation of the post-resection IL13-PE38QQR concentration will be continued until the previously-defined HEC or MTD is reached, after which duration of the post-resection infusion will be increased in one day increments for up to 6 days. If a post-resection MTD is obtained, there will be no increase in duration of infusion. In the final stage of the study, catheters will be placed 2 days after tumor resection, and a 4-day IL13-PE38QQR infusion will begin the day after catheter placement. Patients will be observed clinically and radiographically for toxicity and duration of tumor control.
Detailed description
OBJECTIVES:
- Determine the concentration of IL13-PE38QQR that produces histologic evidence of toxicity to tumor, and the corresponding drug toxicity, following a 2-day continuous infusion into recurrent malignant glioma prior to surgical resection.
II. Determine the toxicity of IL13-PE38QQR administered as a 4-day continuous infusion via catheters into brain adjacent to tumor resection site, after surgical resection, at concentrations up to the selected concentration.
III. Determine the toxicity of increasing duration of continuous infusion of IL13- PE38QQR via catheters into brain adjacent to tumor resection site, after surgical resection, at the selected concentration.
IV. Determine the feasibility and safety of IL13-PE38QQR administration following post-operative placement of stereotaxic catheters 2 days after tumor resection, utilizing a post-operative imaging study for planning of catheter placement. A 4-day continuous infusion at the MTD is planned.
- Describe the time to progression and survival of patients treated with IL13-PE38QQR.
PROTOCOL OUTLINE: This study is designed to determine two dose levels. The first is defined as the histologically effective concentration (HEC) when the agent is administered prior to tumor resection. The second is defined using safety and tolerability of study drug administered after tumor resection at doses up to the HEC. Safety and tolerability of increasing duration of infusion after tumor resection will then be assessed.
Patient cohorts will be treated at escalating pre-resection dose-levels until a stopping criterion for the pre-surgery dose is met, holding the post-resection dose constant at the starting level. Stopping criteria for dose escalation of the pre-surgery infusion are determination of the HEC or the maximum tolerated dose (MTD).
Subsequent cohorts will be treated only post-operatively at escalating dose levels until a stopping criterion for the post-surgery dose is met. Stopping criteria for dose escalation of the post-surgery infusion are reaching the HEC determined for the pre-operative infusion or determination of the MTD. After the HEC is reached, subsequent cohorts will be treated with post-operative infusions of increasing duration at the HEC until the maximum duration defined in the study is reached or an MTD is defined. (If an MTD has already detected, duration will not be escalated.)
After the stage of the study evaluating escalation of infusion duration has completed, the study will expand to evaluate post-operative placement of catheters after tumor resection. This stage of the study will assess the feasibility and safety of stereotaxic placement of catheters 2 days after tumor resection using a post-operative imaging study for planning. Patients will receive a 96 hour post-resection infusion at the MTD.
Cohorts of at least three patients will be entered at each dose level. Each cohort will be observed for at least thirty days after completion of administration of study drug to allow for observation of toxicity before the next cohort is enrolled.
PROJECTED ACCRUAL: Depends on number of dose-levels, estimated at 25-50 patients.
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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites 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, targeted fusion protein therapy and surgery in people with Malignant Glioma and Glioblastoma Multiforme, run by INSYS Therapeutics Inc at 4 sites 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?
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 4 sites 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 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.