Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma: A Phase I/II Study
18 Years
N/A
Both
Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma, Mixed Oligoastrocytoma
Trial Information
Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma: A Phase I/II Study
OBJECTIVES:
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.
Inclusion Criteria
-Disease Characteristics-
Must have prior histologic diagnosis of supratentorial malignant glioma (Grade 3 or 4),
including glioblastoma multiforme, anaplastic astrocytoma, or malignant mixed
oligoastrocytoma (excludes glioma of unknown grade or pure oligodendroglioma). Patients
with clinical/radiographic diagnosis of malignant glioma may be registered pending
histologic confirmation.
Must have undergone prior surgical resection and received external beam radiotherapy with
at least 48 Gy tumor dose, completed at least 8 weeks prior to study.
Must have recurrent or progressive supratentorial tumor compared with a previous study.
Baseline tumor measurements must be determined within 2 weeks prior to study. Stereotaxic
biopsy at study entry must confirm the presence of glioma (malignant, unless previously
known). Recurrent or progressive tumor must have a solid enhancing region at least 1.0 cm
and not more than 6.0 cm in maximum diameter. (One satellite lesion is permitted, if
separated by 3 cm or less from the primary mass.)
-Patient Characteristics-
Age 18 or greater.
Karnofsky Performance Score must be at least 70.
Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 9 gm/dL;
Platelets at least 75,000/mm^3; PT & PTT within institutional limit of normal.
Must be candidate for re-operation.
Must have recovered from toxicity of prior therapy: at least 6 months after approved
intratumoral chemotherapy (e.g. carmustine wafer); at least 6 weeks after
nitrosourea-containing chemotherapy; at least 4 weeks after any investigational agent or
any other cytotoxic chemotherapy; at least 2 weeks after vincristine or non-cytotoxic
chemotherapy.
Must practice an effective method of birth control during the study.
Must understand the investigational nature of this study and its potential risks and
benefits, and sign an approved written informed consent prior to treatment.
No patients with tumor crossing the midline (tumor involving corpus callosum is permitted
if not crossing midline), more than two foci of tumor, or non-parenchymal tumor
dissemination (e.g. subependymal or leptomeningeal).
No patients with impending herniation (e.g. midline shift >1 cm), spinal cord compression,
uncontrolled seizures or requirement for immediate palliative treatment.
No patients who have received localized therapy for glioma, e.g. focal single-fraction
radiotherapy, brachytherapy, or intracerebral infusional chemotherapy.
No patients who are receiving any concurrent chemotherapy or any other investigational
agent (corticiosteroids are permitted).
Female patients must not be pregnant or breast-feeding.
No patients unwilling or unable to follow protocol requirements.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Authority:
United States: Food and Drug Administration
Study ID:
IL13PEI-103
NCT ID:
NCT00041587
Start Date:
July 2002
Completion Date:
July 2007
Related Keywords:
- Malignant Glioma
- Glioblastoma Multiforme
- Anaplastic Astrocytoma
- Mixed Oligoastrocytoma
- Cancer
- Recurrent resectable supratentorial malignant glioma
- Astrocytoma
- Glioblastoma
- Glioma
- Oligodendroglioma
Name | Location |
|---|---|
| Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
| University of Colorado Health Sciences Center | Denver, Colorado 80262 |
