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Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

Primary Purpose

Recurrent Malignant Glioma

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

IL13-PE38QQR

About this trial

This is an interventional treatment trial for Recurrent Malignant Glioma focused on measuring neurosurgery, craniotomy, convection-enhanced delivery, CNS interstitial infusion, recombinant toxins, malignant glioma, recurrent, catheter,, intratumoral therapy, positive pressure microinfusion

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

-Disease Characteristics-

Must be at least 3 years but not more than 21 years of age.

Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma, mixed anaplastic astrocytoma, or glioblastoma multiforme.

Must have radiographic evidence of recurrent or progressive supratentorial malignant glioma compared with a prior imaging study. The baseline tumor measurements must be determined within 2 weeks prior to study entry.

The tumor must have a solid component at least 1.0 cm in diameter.

Gross total resection must be planned, with the intent of removing all contrast-enhancing components of the tumor.

Must have received external beam radiotherapy, with tumor dose of at least 48 Gy; and must be completed at least 8 weeks prior to study entry.

-Patient Characteristics-

Karnofsky Performance Score for patients older than 16 years, or the Lansky Performance Scale for patients 16 years old or younger, must be at least 60.

Hematologic status: Absolute neutrophils at least 1,500/mm3; Hemoglobin at least 10 gm/dL (transfusion independent); Platelets at least 100,000/mm3 (transfusion independent); PT & aPTT less than or equal to the institutional upper limit of normal.

Must have recovered from toxicity of prior therapy: at least 6 months after Gliadel® wafer; at least 8 weeks after hematopoietic stem cell transplant; at least 4 weeks after any cytotoxic chemotherapy or any systemic investigational agent; at least 6 weeks after nitrosoureas; at least 2 weeks after vincristine or non-cytotoxic chemotherapy.

Patient's legal guardian must understand the investigational nature of this study and its potential risks and benefits; must sign informed consent.

No pregnant or breast-feeding patients. All patients of child-bearing age, male and female, must practice an effective method of birth control during the study.

No patients with multi-focal tumor not amenable to gross total resection or tumor dissemination (subependymal or leptomeningeal).

No patients with clinically significant increased intracranial pressure (e.g., impending herniation) uncontrolled seizures, or requirement for immediate palliative treatment.

No patients who received any localized antitumor therapy for the malignant glioma, either intracerebral chemotherapy (other than Gliadel®) or focal radiation therapy (e.g., stereotactic radiosurgery or brachytherapy).

No patients who are receiving concurrent chemotherapy (other than steroids) or any other investigational agent.

No patients unwilling to follow protocol requirements.

Sites / Locations

University of California San Francisco
Children's National Medical Center
Children's Memorial Hospital
Dana-Farber Cancer Institute-Dept of Pediatric Oncology
Duke University Medical Center-Dept. of Pediatrics, Medicine & Surgery
The Children's Hospital of Philadelphia
Children's Hospital of Pittsburgh
St. Jude Children's Research Hospital
Baylor College of Medicine-Dept of Pediatrics
Children's Hospital & Regional Medical Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00378235

First Posted

September 18, 2006

Last Updated

November 11, 2014

Sponsor

INSYS Therapeutics Inc

Collaborators

Pediatric Brain Tumor Consortium (PBTC), St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00378235

Brief Title

Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

Official Title

Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Withdrawn

Why Stopped

There was a change of sponsor. The new sponsor company did not wish to conduct the study after all.

Study Start Date

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Primary Completion Date

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Study Completion Date

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3. Sponsor/Collaborators

Name of the Sponsor

INSYS Therapeutics Inc

Collaborators

Pediatric Brain Tumor Consortium (PBTC), St. Jude Children's Research Hospital

4. Oversight

5. Study Description

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.

Detailed Description

PHASE I OBJECTIVES: I. To describe toxicities and estimate the maximum safe flow rate and maximum tolerated infusion concentration, of IL13-PE38QQR delivered after surgical resection by peritumoral infusion via 2 to 4 catheters positioned in the brain adjacent to the resection cavity, from the start of infusion through the DLT observation period. II. To determine the IL13 receptor alpha-2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas. III. To describe the overall safety and tolerability of IL13PE38QQR infusion from the start of infusion through disease progression or initiation of alternative treatment. PHASE II OBJECTIVES: I. To estimate the survival distribution post initial progression, at the maximum safe total flow rate and MTiC established in phase I. II. To estimate the progression-free survival distribution for patients post-initial progression or recurrence at the maximum safe total flow rate and MTiC established in phase I. III. To determine the serum levels of IL13-PE38QQR and distribution in pediatric recurrent or progressive malignant gliomas. IV. To describe the overall safety and tolerability of IL13-PE38QQR infusion from the start of infusion through disease progression or initiation of alternative treatment. PROTOCOL OUTLINE: At study entry, all patients will be registered prior to planned gross total resection (> 95% resection of the solid, contrast enhancing tumor component). On the day of catheter placement (CP, 2-7 days after resection), if the patient is neurologically stable, 2-4 catheters will be stereotactically placed. On day 1 after catheter placement, infusion of IL3-PE38QQR will begin if the patient is neurologically stable and will continue for 96 hours. In Phase I, the total flow rate and the concentration of IL3-PE38QQR will be determined by the dose escalation plan. In the Phase II evaluations of safety and efficacy, patients will be treated at the flow rate and concentration identified in Phase I. PROJECTED ACCRUAL: Approximately 24 patients will participate in the Phase I portion of the study. During the Phase I portion, the rate-limiting factor is the time the study must be closed during the toxicity assessment period. Although it is estimated that 1.5 patients per month will enroll in the Phase I portion, the observed rate may be lower due to temporary suspensions in accrual. It is not possible to estimate the time required to complete the Phase I portion of the trial. It is estimated that approximately 26 patients will contribute to the Phase II portion. Using the same rough estimate of accrual, the Phase II portion may last about 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Malignant Glioma

Keywords

neurosurgery, craniotomy, convection-enhanced delivery, CNS interstitial infusion, recombinant toxins, malignant glioma, recurrent, catheter,, intratumoral therapy, positive pressure microinfusion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

IL13-PE38QQR

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

-Disease Characteristics- Must be at least 3 years but not more than 21 years of age. Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma, mixed anaplastic astrocytoma, or glioblastoma multiforme. Must have radiographic evidence of recurrent or progressive supratentorial malignant glioma compared with a prior imaging study. The baseline tumor measurements must be determined within 2 weeks prior to study entry. The tumor must have a solid component at least 1.0 cm in diameter. Gross total resection must be planned, with the intent of removing all contrast-enhancing components of the tumor. Must have received external beam radiotherapy, with tumor dose of at least 48 Gy; and must be completed at least 8 weeks prior to study entry. -Patient Characteristics- Karnofsky Performance Score for patients older than 16 years, or the Lansky Performance Scale for patients 16 years old or younger, must be at least 60. Hematologic status: Absolute neutrophils at least 1,500/mm3; Hemoglobin at least 10 gm/dL (transfusion independent); Platelets at least 100,000/mm3 (transfusion independent); PT & aPTT less than or equal to the institutional upper limit of normal. Must have recovered from toxicity of prior therapy: at least 6 months after Gliadel® wafer; at least 8 weeks after hematopoietic stem cell transplant; at least 4 weeks after any cytotoxic chemotherapy or any systemic investigational agent; at least 6 weeks after nitrosoureas; at least 2 weeks after vincristine or non-cytotoxic chemotherapy. Patient's legal guardian must understand the investigational nature of this study and its potential risks and benefits; must sign informed consent. No pregnant or breast-feeding patients. All patients of child-bearing age, male and female, must practice an effective method of birth control during the study. No patients with multi-focal tumor not amenable to gross total resection or tumor dissemination (subependymal or leptomeningeal). No patients with clinically significant increased intracranial pressure (e.g., impending herniation) uncontrolled seizures, or requirement for immediate palliative treatment. No patients who received any localized antitumor therapy for the malignant glioma, either intracerebral chemotherapy (other than Gliadel®) or focal radiation therapy (e.g., stereotactic radiosurgery or brachytherapy). No patients who are receiving concurrent chemotherapy (other than steroids) or any other investigational agent. No patients unwilling to follow protocol requirements.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anuradha Banerjee, MD, MPH

Organizational Affiliation

University of California at San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Children's National Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Children's Memorial Hospital

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60614

Country

United States

Facility Name

Dana-Farber Cancer Institute-Dept of Pediatric Oncology

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Duke University Medical Center-Dept. of Pediatrics, Medicine & Surgery

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

The Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Children's Hospital of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38014

Country

United States

Facility Name

Baylor College of Medicine-Dept of Pediatrics

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Children's Hospital & Regional Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

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