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
- 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
- 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
- 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
PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be
accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Roger J. Packer, MD
Children's Research Institute
United States: Food and Drug Administration
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|