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IL13-PE38QQR Infusion After Tumor Resection, Followed by Radiation Therapy With or Without Temozolomide in Patients With Newly Diagnosed Malignant Glioma

Primary Purpose

Glioblastoma Multiforme, Anaplastic Astrocytoma, Oligoastrocytoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IL13-PE38QQR
Surgery for placement
Radiation therapy
Temozolomide with radiation therapy
Sponsored by
INSYS Therapeutics Inc
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring brain tumor, malignant glioma, brain neoplasm, central nervous system, surgery, resection, temozolomide, infusion, glioblastoma multiforme, anaplastic astrocytoma, oligoastrocytoma, Temodar, radiation, convection-enhanced delivery, GBM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must be ≥18 years old. Patients must have undergone a gross total resection of the solid contrast-enhancing lesion(s) > 1.0 cm in diameter. Patients must be able to have catheters placed within 14 days of tumor resection (including a planned Gross Total Resection following an initial biopsy or subtotal resection) Patients must have histopathologic confirmation of malignant glioma from resection specimen. Diagnosis must be consistent with either GBM, AA, or malignant mixed OA. Patients must be in adequate general condition and meet the following criteria: a. Karnofsky Performance Scale score ≥ 70 b. Adequate hematologic status: Absolute neutrophil count ≥ 1,500/mm³ Hemoglobin ≥ 10 gm/dL Platelets ≥ 100,000/mm³ PT & aPTT within institutional limits of normal Female patients must not be pregnant or breast-feeding. Patients must practice an effective method of birth control during the study and for 60 days beyond the last day of infusion. Patients must understand the investigational nature of this study and its potential risks and benefits, and sign an approved written informed consent prior to performance of any study-specific procedure. Exclusion Criteria: Patients with residual contrast-enhancing tumor crossing the midline, multifocal tumor not amenable to gross total resection or non-parenchymal tumor dissemination (e.g., subependymal or leptomeningeal). Patients with clinically significant increased ICP (e.g., impending herniation), uncontrolled seizures or requirement for immediate palliative treatment. Patients who have received any prior anti-tumor treatment (other than corticosteroids) including any investigational agents. Patients with any metallic prosthesis that would prevent MRI and/or MRS scanning procedures of the brain. Patients unwilling or unable to follow protocol requirements.

Sites / Locations

  • University of California San Francisco - Dept. of Neurological Surgery
  • Carolina Neurosurgery & Spine Assoc.
  • Duke University Medical Center
  • Cleveland Clinic Foundation Department of Neurological Surgery
  • University of Texas M.D. Anderson Cancer Center
  • University of Virginia Health Systems - Department of Neurological Surgery

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
August 5, 2004
Last Updated
June 30, 2011
Sponsor
INSYS Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT00089427
Brief Title
IL13-PE38QQR Infusion After Tumor Resection, Followed by Radiation Therapy With or Without Temozolomide in Patients With Newly Diagnosed Malignant Glioma
Official Title
Phase I Study of Convection Enhanced Delivery (CED) of IL13-PE38QQR Infusion After Resection Followed by Radiation Therapy With or Without Temozolomide in Patients With Newly Diagnosed Supratentorial Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
INSYS Therapeutics Inc

4. Oversight

5. Study Description

Brief Summary
This Phase 1 study in patients with newly diagnosed malignant glioma is designed to determine the highest dose of IL13-PE38QQR that can be safely administered by Convection Enhanced Delivery (CED) to the area around the tumor site after the tumor is surgically removed (resection). In addition, the patient will receive radiation therapy and may or may not be treated with oral temozolomide.
Detailed Description
This is a Phase I clinical trial of experimental drug IL13-PE38QQR (Study Drug) in patients with newly diagnosed malignant glioma. IL13-PE38QQR is a tumor-targeting agent administered by a continuous infusion directly into the brain around the cavity where the tumor has been removed. Through previous research, this Study Drug has shown potential to control some of the recurrent malignant gliomas, such as glioblastoma multiforme (GBM), anaplastic astrocytoma, and malignant mixed oligoastrocytoma. The Study Drug is made by combining a human protein (IL13) with a portion of a bacterial toxin protein, Pseudomonas Exotoxin (PE). The IL13 portion binds to receptors on the tumor like a "key to a lock," allowing the PE portion to enter and kill those cells. Since tumor cells preferentially bind the drug, normal (healthy) brain cells are much less likely to be damaged by the drug. The Study Drug is delivered through tubing or catheters placed directly into the area surrounding the resection cavity. These catheters will be surgically placed within 14 days after the tumor has been removed. A pump is then used to slowly push the drug solution through the catheters using convection-enhanced delivery (CED) over a period of 4 days. Following treatment with IL13-PE38QQR, all patients will receive standard courses of radiation therapy. In addition, some patients will receive adjuvant temozolomide with radiation therapy and continue with temozolomide after radiation therapy is completed. Temozolomide is an anti-cancer drug that is approved by the U.S. Food and Drug Administration (FDA) and sold for the treatment of recurrent GBM. This study will determine the maximum tolerated dose of IL13-PE38QQR when administered by CED after tumor resection and prior to radiation therapy with or without adjuvant temozolomide. Patients with newly diagnosed malignant glioma who have had a gross total resection of their tumor and who meet all other specified eligibility criteria may be entered into the study. Patients will be divided into 2 groups: Stratum A - will receive treatment with IL13-PE38QQR followed by radiation therapy and Stratum B - will receive treatment with IL13-PE38QQR followed by radiation therapy with adjuvant temozolomide. Treatment with temozolomide for Stratum B will continue after radiation therapy is completed. Subgroups (cohorts) of patients will be treated with up to 3 doses of IL13-PE38QQR. Cohorts of 3-6 patients will be treated at each dose level. Enrollment into each subsequent cohort will be dependent upon the safety and tolerability of treatment in the previous cohort. All patients will need to have histopathological confirmation of malignant glioma diagnosis from tissue sample obtained at the time of gross total resection within 14 days of stereotactic catheter placement. Each patient will have 2-4 standard microinfusion catheters placed and infusion of IL13-PE38QQR will begin within 24 hours of catheter placement. The infusion will last for 96 hours. Approximately 2 weeks after completion of infusion, imaging for radiation therapy planning, a physical examination, and neurological and laboratory assessments will be performed. Patients, if stable, will then receive standard fractionated external beam radiation therapy with a total dose between 5940-6100 cGy using 180 to 200 cGy per fraction. For those patients assigned to receive temozolomide in combination with radiation therapy, the dose of temozolomide will be administered on each day of radiation therapy and will be based on the patient's body surface area BSA at a dose of 75 mg/m²/day. After radiation therapy is completed and the follow-up MRI has revealed stable disease or a response, patients will continue temozolomide using repeat scheduled dosing at 150 -200 mg/m²/day for 5 consecutive days per 28 day cycle. Treatment cycles will continue for up to 12 cycles.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Anaplastic Astrocytoma, Oligoastrocytoma
Keywords
brain tumor, malignant glioma, brain neoplasm, central nervous system, surgery, resection, temozolomide, infusion, glioblastoma multiforme, anaplastic astrocytoma, oligoastrocytoma, Temodar, radiation, convection-enhanced delivery, GBM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
IL13-PE38QQR
Intervention Type
Procedure
Intervention Name(s)
Surgery for placement
Intervention Type
Procedure
Intervention Name(s)
Radiation therapy
Intervention Type
Drug
Intervention Name(s)
Temozolomide with radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be ≥18 years old. Patients must have undergone a gross total resection of the solid contrast-enhancing lesion(s) > 1.0 cm in diameter. Patients must be able to have catheters placed within 14 days of tumor resection (including a planned Gross Total Resection following an initial biopsy or subtotal resection) Patients must have histopathologic confirmation of malignant glioma from resection specimen. Diagnosis must be consistent with either GBM, AA, or malignant mixed OA. Patients must be in adequate general condition and meet the following criteria: a. Karnofsky Performance Scale score ≥ 70 b. Adequate hematologic status: Absolute neutrophil count ≥ 1,500/mm³ Hemoglobin ≥ 10 gm/dL Platelets ≥ 100,000/mm³ PT & aPTT within institutional limits of normal Female patients must not be pregnant or breast-feeding. Patients must practice an effective method of birth control during the study and for 60 days beyond the last day of infusion. Patients must understand the investigational nature of this study and its potential risks and benefits, and sign an approved written informed consent prior to performance of any study-specific procedure. Exclusion Criteria: Patients with residual contrast-enhancing tumor crossing the midline, multifocal tumor not amenable to gross total resection or non-parenchymal tumor dissemination (e.g., subependymal or leptomeningeal). Patients with clinically significant increased ICP (e.g., impending herniation), uncontrolled seizures or requirement for immediate palliative treatment. Patients who have received any prior anti-tumor treatment (other than corticosteroids) including any investigational agents. Patients with any metallic prosthesis that would prevent MRI and/or MRS scanning procedures of the brain. Patients unwilling or unable to follow protocol requirements.
Facility Information:
Facility Name
University of California San Francisco - Dept. of Neurological Surgery
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Carolina Neurosurgery & Spine Assoc.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic Foundation Department of Neurological Surgery
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virginia Health Systems - Department of Neurological Surgery
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States

12. IPD Sharing Statement

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IL13-PE38QQR Infusion After Tumor Resection, Followed by Radiation Therapy With or Without Temozolomide in Patients With Newly Diagnosed Malignant Glioma

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