Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00041587
Status:
COMPLETED
Last Update Posted:
2011-06-06
First Post:
2002-07-10
Brief Title:
Pre-operative IL13-PE38QQR in Patients With Recurrent or Progressive Malignant Glioma
Sponsor:
INSYS Therapeutics Inc
Organization:
INSYS Therapeutics Inc
Study Overview
Official Title:
Pre-operative IL13-PE38QQR Infusion in Patients With Recurrent or Progressive Supratentorial Malignant Glioma A Phase III Study
Status:
COMPLETED
Status Verified Date:
2011-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
IL13-PE38QQR is an oncology drug product consisting of IL13 interleukin-13 and PE38QQR a bacteria toxin IL13-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
Prior to treatment patients will have physical and neurologic exams MRI to measure the extent of tumor tumor biopsy and screening laboratory tests On Day 1 one or two catheters will be inserted directly into the tumor after which a CT scan will be used to confirm placement Each patient will receive one IL13-PE38QQR infusion and the tumor will be surgically removed on approximately Day 15 In the first group of patients IL13-PE38QQR will be infused directly into the tumor for 4 days Depending on effectiveness or side effects of the study drug the duration will be increased stepwise to a maximum of 7 days in subsequent groups of patients Once duration of infusion has been determined the dose of IL13-PE38QQR will be increased stepwise in separate groups of patients depending on effectiveness or side effects of the study drug The activity of the drug against the tumor cells will be judged by examining the removed tumor tissue Patients will have neurologic exams and MRI scans immediately after the resection and every eight weeks until disease progression is observed
Prior to treatment patients will have physical and neurologic exams MRI to measure the extent of tumor tumor biopsy and screening laboratory tests On Day 1 one or two catheters will be inserted directly into the tumor after which a CT scan will be used to confirm placement Each patient will receive one IL13-PE38QQR infusion and the tumor will be surgically removed on approximately Day 15 In the first group of patients IL13-PE38QQR will be infused directly into the tumor for 4 days Depending on effectiveness or side effects of the study drug the duration will be increased stepwise to a maximum of 7 days in subsequent groups of patients Once duration of infusion has been determined the dose of IL13-PE38QQR will be increased stepwise in separate groups of patients depending on effectiveness or side effects of the study drug The activity of the drug against the tumor cells will be judged by examining the removed tumor tissue Patients will have neurologic exams and MRI scans immediately after the resection and every eight weeks until disease progression is observed
Detailed Description:
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 mLhr 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 518 mL 4 days to a maximum of 907 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 907 mg to a maximum of 3628 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
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 mLhr 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 518 mL 4 days to a maximum of 907 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 907 mg to a maximum of 3628 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None