Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00024557
Status:
COMPLETED
Last Update Posted:
2011-06-06
First Post:
2001-09-20
Brief Title:
Histologic EffectSafety of PrePost-Operative IL13-PE38QQR in Recurrent Resectable Supratentorial Malignant Glioma Patients
Sponsor:
INSYS Therapeutics Inc
Organization:
INSYS Therapeutics Inc
Study Overview
Official Title:
Phase I Study to Assess the Histologic Effect and Safety of Pre-Operative and Post-Operative Infusions of IL13-PE38QQR Cytotoxin in Patients With Recurrent Resectable Supratentorial Malignant Glioma
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 IL3-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
Patients will receive IL13-PE38QQR via a catheter placed directly into the brain tumor Tumor recurrence will be confirmed by biopsy The next day patients will start a continuous 48-hour infusion of IL13-PE38QQR into the tumor The dose concentration will be increased in the pre-resection infusion until the endpoint is reached histologic evidence of tumor cytotoxicity or a maximum tolerated dose Tumor resection will be planned for one week after biopsy plus or minus 1 day A histologically-effective concentration HEC will be determined using pathologic observations At the end of resection three catheters will be placed in brain tissue next to the resection site and assessed within 24 hours using MRI On the second day after surgery IL13-PE38QQR infusion will begin and will continue for 4 days The lowest pre-resection IL13-PE38QQR concentration will be used as the starting dose for post-resection infusions After an HEC or maximum tolerated dose MTD is determined the pre-resection infusion will no longer be administered Subsequent patients will have tumor resection and placement of three peri-tumoral catheters at study entry IL13-PE38QQR will be infused starting on the second day after surgery and continuing for 4 days Escalation of the post-resection IL13-PE38QQR concentration will be continued until the previously-defined HEC or MTD is reached after which duration of the post-resection infusion will be increased in one day increments for up to 6 days If a post-resection MTD is obtained there will be no increase in duration of infusion In the final stage of the study catheters will be placed 2 days after tumor resection and a 4-day IL13-PE38QQR infusion will begin the day after catheter placement Patients will be observed clinically and radiographically for toxicity and duration of tumor control
Patients will receive IL13-PE38QQR via a catheter placed directly into the brain tumor Tumor recurrence will be confirmed by biopsy The next day patients will start a continuous 48-hour infusion of IL13-PE38QQR into the tumor The dose concentration will be increased in the pre-resection infusion until the endpoint is reached histologic evidence of tumor cytotoxicity or a maximum tolerated dose Tumor resection will be planned for one week after biopsy plus or minus 1 day A histologically-effective concentration HEC will be determined using pathologic observations At the end of resection three catheters will be placed in brain tissue next to the resection site and assessed within 24 hours using MRI On the second day after surgery IL13-PE38QQR infusion will begin and will continue for 4 days The lowest pre-resection IL13-PE38QQR concentration will be used as the starting dose for post-resection infusions After an HEC or maximum tolerated dose MTD is determined the pre-resection infusion will no longer be administered Subsequent patients will have tumor resection and placement of three peri-tumoral catheters at study entry IL13-PE38QQR will be infused starting on the second day after surgery and continuing for 4 days Escalation of the post-resection IL13-PE38QQR concentration will be continued until the previously-defined HEC or MTD is reached after which duration of the post-resection infusion will be increased in one day increments for up to 6 days If a post-resection MTD is obtained there will be no increase in duration of infusion In the final stage of the study catheters will be placed 2 days after tumor resection and a 4-day IL13-PE38QQR infusion will begin the day after catheter placement Patients will be observed clinically and radiographically for toxicity and duration of tumor control
Detailed Description:
OBJECTIVES
I Determine the concentration of IL13-PE38QQR that produces histologic evidence of toxicity to tumor and the corresponding drug toxicity following a 2-day continuous infusion into recurrent malignant glioma prior to surgical resection
II Determine the toxicity of IL13-PE38QQR administered as a 4-day continuous infusion via catheters into brain adjacent to tumor resection site after surgical resection at concentrations up to the selected concentration
III Determine the toxicity of increasing duration of continuous infusion of IL13- PE38QQR via catheters into brain adjacent to tumor resection site after surgical resection at the selected concentration
IV Determine the feasibility and safety of IL13-PE38QQR administration following post-operative placement of stereotaxic catheters 2 days after tumor resection utilizing a post-operative imaging study for planning of catheter placement A 4-day continuous infusion at the MTD is planned
V Describe the time to progression and survival of patients treated with IL13-PE38QQR
PROTOCOL OUTLINE This study is designed to determine two dose levels The first is defined as the histologically effective concentration HEC when the agent is administered prior to tumor resection The second is defined using safety and tolerability of study drug administered after tumor resection at doses up to the HEC Safety and tolerability of increasing duration of infusion after tumor resection will then be assessed
Patient cohorts will be treated at escalating pre-resection dose-levels until a stopping criterion for the pre-surgery dose is met holding the post-resection dose constant at the starting level Stopping criteria for dose escalation of the pre-surgery infusion are determination of the HEC or the maximum tolerated dose MTD
Subsequent cohorts will be treated only post-operatively at escalating dose levels until a stopping criterion for the post-surgery dose is met Stopping criteria for dose escalation of the post-surgery infusion are reaching the HEC determined for the pre-operative infusion or determination of the MTD After the HEC is reached subsequent cohorts will be treated with post-operative infusions of increasing duration at the HEC until the maximum duration defined in the study is reached or an MTD is defined If an MTD has already detected duration will not be escalated
After the stage of the study evaluating escalation of infusion duration has completed the study will expand to evaluate post-operative placement of catheters after tumor resection This stage of the study will assess the feasibility and safety of stereotaxic placement of catheters 2 days after tumor resection using a post-operative imaging study for planning Patients will receive a 96 hour post-resection infusion at the MTD
Cohorts of at least three patients will be entered at each dose level Each cohort will be observed for at least thirty days after completion of administration of study drug to allow for observation of toxicity before the next cohort is enrolled
PROJECTED ACCRUAL Depends on number of dose-levels estimated at 25-50 patients
I Determine the concentration of IL13-PE38QQR that produces histologic evidence of toxicity to tumor and the corresponding drug toxicity following a 2-day continuous infusion into recurrent malignant glioma prior to surgical resection
II Determine the toxicity of IL13-PE38QQR administered as a 4-day continuous infusion via catheters into brain adjacent to tumor resection site after surgical resection at concentrations up to the selected concentration
III Determine the toxicity of increasing duration of continuous infusion of IL13- PE38QQR via catheters into brain adjacent to tumor resection site after surgical resection at the selected concentration
IV Determine the feasibility and safety of IL13-PE38QQR administration following post-operative placement of stereotaxic catheters 2 days after tumor resection utilizing a post-operative imaging study for planning of catheter placement A 4-day continuous infusion at the MTD is planned
V Describe the time to progression and survival of patients treated with IL13-PE38QQR
PROTOCOL OUTLINE This study is designed to determine two dose levels The first is defined as the histologically effective concentration HEC when the agent is administered prior to tumor resection The second is defined using safety and tolerability of study drug administered after tumor resection at doses up to the HEC Safety and tolerability of increasing duration of infusion after tumor resection will then be assessed
Patient cohorts will be treated at escalating pre-resection dose-levels until a stopping criterion for the pre-surgery dose is met holding the post-resection dose constant at the starting level Stopping criteria for dose escalation of the pre-surgery infusion are determination of the HEC or the maximum tolerated dose MTD
Subsequent cohorts will be treated only post-operatively at escalating dose levels until a stopping criterion for the post-surgery dose is met Stopping criteria for dose escalation of the post-surgery infusion are reaching the HEC determined for the pre-operative infusion or determination of the MTD After the HEC is reached subsequent cohorts will be treated with post-operative infusions of increasing duration at the HEC until the maximum duration defined in the study is reached or an MTD is defined If an MTD has already detected duration will not be escalated
After the stage of the study evaluating escalation of infusion duration has completed the study will expand to evaluate post-operative placement of catheters after tumor resection This stage of the study will assess the feasibility and safety of stereotaxic placement of catheters 2 days after tumor resection using a post-operative imaging study for planning Patients will receive a 96 hour post-resection infusion at the MTD
Cohorts of at least three patients will be entered at each dose level Each cohort will be observed for at least thirty days after completion of administration of study drug to allow for observation of toxicity before the next cohort is enrolled
PROJECTED ACCRUAL Depends on number of dose-levels estimated at 25-50 patients
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