Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma: A Phase I/II Study
I. 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
United States: Food and Drug Administration
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|University of Colorado Health Sciences Center||Denver, Colorado 80262|