Brain and Central Nervous System TumorsPhase 1/2NCT00074334
TP-38 Toxin in Treating Young Patients With Recurrent or Progressive Supratentorial High-Grade Glioma
A Phase 1/2 study testing TGFa-PE38 immunotoxin and conventional surgery in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 8 sites in United States.
Trial summary
RATIONALE: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works… 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?
- TGFa-PE38 immunotoxin and conventional surgery
- Type of treatment
- Surgery or procedure
- How many people
- 3 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2004to Jun 2006
- 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 supratentorial malignant glioma
- Recurrent or progressive disease
- Amenable to gross total resection, clinically indicated partial resection, or biopsy
- Tumor must have a single solid portion at least 1 cm and no greater than 5 cm in maximum diameter
- No tumor crossing midline
- Tumors invading the corpus callosum that do not extend beyond to midline or into the contralateral hemisphere allowed
- No more than 1 focus of tumor
- No tumors involving the brainstem or cerebellum
- No tumor dissemination (i.e., subependymal or leptomeningeal)
- Must be on steroids ≥ 3 days prior to surgery
- Must have received prior external beam radiotherapy (tumor dose at least 45 Gy) and completed therapy at least 8 weeks before study entry
- No impending herniation, including midline shift greater than 0.5 cm
- No requirement for immediate palliative treatment
PATIENT CHARACTERISTICS:
Age
- 3 to 21
Performance status
- Karnofsky 60-100% (patients over 16 years of age) OR
- Lansky 60-100% (patients age 16 and under)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3*
- Hemoglobin at least 9 g/dL* NOTE: *Transfusion independent
Hepatic
- ALT and AST less than 2.5 times upper limit of normal (ULN)
- PT and PTT no greater than ULN
Renal
- Creatinine less than 1.5 times normal OR
- Glomerular filtration rate greater than 70 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 30 days after study participation
- No uncontrolled seizures
- No active infection requiring treatment
- No unexplained febrile illness
- No known or suspected allergies to local anesthetics
- No systemic disease or other condition that may be associated with unacceptable anesthetic/operative risk and/or that would preclude study completion
- No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 8 weeks since prior hematopoietic stem cell transplantation
Chemotherapy
- At least 6 months since prior polifeprosan 20 with carmustine implant (Gliadel® wafer)
- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas and 2 weeks for vincristine)
- At least 2 weeks since prior non-cytotoxic chemotherapy
- No other prior intracerebral chemotherapy
- No concurrent chemotherapy
Endocrine therapy
- Concurrent steroids allowed
Radiotherapy
- See Disease Characteristics
- No prior focal radiotherapy (e.g., gamma knife radiosurgery, stereotactic radiosurgery, or brachytherapy)
- No concurrent radiotherapy
Surgery
- Not specified
Other
- Recovered from prior therapy
- At least 4 weeks since prior anticancer investigational agents
- No prior localized antitumor therapy for malignant glioma
- No other concurrent investigational agent
- No other concurrent anticancer (including alternative anticancer medicines/treatment) agent or therapy
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
Official title: A Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas
RATIONALE: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works in treating young patients with recurrent or progressive supratentorial high-grade glioma.
Read the detailed description
OBJECTIVES:
Primary
- Phase I
- Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
- Describe the toxic effects of this drug in these patients.
- Phase II
- Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients.
Secondary
- Phase I and II
- Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
- Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug.
- Phase II Only
- Estimate the objective response rate in patients treated with this drug.
- Estimate the progression-free survival of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and by surgery extent (surgical resection vs stereotactic biopsy) for those with first recurrence only.
- Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients (in each stratum) receive escalating volumes until the maximum safe volume (MSV) is determined. Cohorts of 3-6 patients (in each stratum) receive escalating concentrations at the MSV until the maximum tolerated infusion concentration (MTIC) is determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive treatment as in phase I at the MSV and MTIC.
Phase I patients are followed post catheter placement, daily during TP-38 infusion, at 30 days, and then every 2 months for 1 year. Phase II patients will be followed for an additional year.
PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- TGFa-PE38 immunotoxin, conventional surgery
- Keywords
- childhood high-grade cerebral astrocytoma, recurrent childhood cerebral astrocytoma, childhood oligodendroglioma, childhood supratentorial ependymoma, recurrent childhood ependymoma, recurrent childhood brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma, Oligodendroglioma, Familial ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGFa-PE38 immunotoxinBiological
conventional surgeryProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Toxicities of TP-38
Post-infusion survival (phase II)
Secondary outcomes (4)
EGFR expression and phosphorylation (activity)
Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II).
Post-infusion progression-free survival (phase II)
Objective response (phase II)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2003 (estimated)
- Study startMay 2004
- Primary completionJun 2006
- Study completionJun 2006
Why it stopped: Drug company withdrawal of support for investigational agent in this indication.
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
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Roger J. Packer, MD, Study chair, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00074334
- Sponsor's protocol ID
- CDR0000344416
- Other IDs
- PBTC-013
- Status last verified
- Oct 2009
- First submitted
- 10 Dec 2003
- Last updated
- 21 Oct 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas
- ClinicalTrials.gov ID
- NCT00074334
- Acronym / sponsor ID
- CDR0000344416
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- childhood high-grade cerebral astrocytoma, recurrent childhood cerebral astrocytoma, childhood oligodendroglioma, childhood supratentorial ependymoma, recurrent childhood ependymoma, recurrent childhood brain tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug company withdrawal of support for investigational agent in this indication.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2004
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jun 2006 (actual)
- First posted
- 11 Dec 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: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works in treating young patients with recurrent or progressive supratentorial high-grade glioma.
Detailed description
OBJECTIVES:
Primary
- Phase I
- Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
- Describe the toxic effects of this drug in these patients.
- Phase II
- Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients.
Secondary
- Phase I and II
- Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
- Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug.
- Phase II Only
- Estimate the objective response rate in patients treated with this drug.
- Estimate the progression-free survival of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and by surgery extent (surgical resection vs stereotactic biopsy) for those with first recurrence only.
- Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients (in each stratum) receive escalating volumes until the maximum safe volume (MSV) is determined. Cohorts of 3-6 patients (in each stratum) receive escalating concentrations at the MSV until the maximum tolerated infusion concentration (MTIC) is determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive treatment as in phase I at the MSV and MTIC.
Phase I patients are followed post catheter placement, daily during TP-38 infusion, at 30 days, and then every 2 months for 1 year. Phase II patients will be followed for an additional year.
PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.
Study design
- Primary purpose
- Treatment
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 |
|---|---|---|
| TGFa-PE38 immunotoxin | Biological | – |
| conventional surgery | Procedure or surgery | – |
Primary outcome
Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Toxicities of TP-38
Post-infusion survival (phase II)
4 secondary outcomes
EGFR expression and phosphorylation (activity)
Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II).
Post-infusion progression-free survival (phase II)
Objective response (phase II)
Results and safety
The study was stopped early (reason given: Drug company withdrawal of support for investigational agent in this indication.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2009.
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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.
Roger J. Packer, MD study chair
Children's National Research Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TGFa-PE38 immunotoxin and conventional surgery in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 8 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: stopped early, as of the sponsor's last update on 21 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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 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 stopped early (reason given: Drug company withdrawal of support for investigational agent in this indication.). 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?
Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).. 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 21 Oct 2009.