Immunotoxin Therapy in Treating Children With Recurrent Malignant Gliomas - Full Text View

Sponsors and Collaborators:	Pediatric Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00053040

Purpose

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: cintredekin besudotox Procedure: conventional surgery	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase I/II Trial Of Intracerebral IL13-PE38QQR Infusions In Pediatric Patients With Recurrent Malignant Glioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Cintredekin Besudotox

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity (Phase I) [ Designated as safety issue: Yes ]
Maximum safe flow rate (Phase I) [ Designated as safety issue: No ]
Maximum tolerated infusion concentration (Phase I) [ Designated as safety issue: No ]
Survival distribution post initial recurrence or progression at the maximum safe total flow rate at maximum tolerated infusion concentration (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival (Phase II) [ Designated as safety issue: No ]
IL13receptor α2 chain expression status and distribution [ Designated as safety issue: No ]
Overall safety [ Designated as safety issue: Yes ]
Tolerability [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	October 2005

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
Determine the rate of survival after initial progression in patients treated at the maximum flow rate and MTiC with this drug. (Phase II)

Secondary

Determine the overall safety and tolerability of this regimen in these patients.
Determine the progression-free survival of patients treated with this drug. (Phase II)

OUTLINE: This is a multicenter, dose-escalation study.

Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later, patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed after completion of the infusion.

Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed concentration until the maximum safe flow rate is determined. The maximum safe flow rate is defined as the rate prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive IL13-PE38QQR at escalating concentrations and a fixed flow rate until the maximum tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the concentration prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

Phase II: Patients receive IL13-PE38QQR as above at the MTiC. Patients are followed at week 18 and then every 8-12 weeks thereafter.

PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for phase II) will be accrued for this study.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed grade 3 or 4 supratentorial malignant glioma by prior surgery or biopsy
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Malignant mixed oligoastrocytoma
Recurrent or progressive disease by radiology
- In first progression or recurrence (for patients in the phase II portion of the study only)
Must have 1 solid primary lesion with a solid component measuring at least 1 cm in diameter
Must have received external beam radiotherapy with tumor dose of at least 48 Gy
Planning to undergo gross total resection of the tumor to remove all contrast-enhancing components of the tumor
- No multifocal tumor not amenable to gross tumor resection
No contrast-enhancing tumor component crossing the midline
No subependymal or leptomeningeal tumor dissemination
No clinically significant increased intracranial pressure (e.g., impending herniation)
No spinal cord compression
No requirement for immediate palliative treatment

PATIENT CHARACTERISTICS:

Age

3 to 21

Performance status

Karnofsky 60-100% (over 16 years of age)
Lansky 60-100 (16 years of age and under)

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Hemoglobin at least 10 g/dL*
Platelet count at least 100,000/mm^3* NOTE: *Transfusion independent

Hepatic

PT and PTT normal

Renal

Creatinine normal for age

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled seizures

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 8 weeks since prior hematopoietic stem cell transplantation

Chemotherapy

No prior intracerebral chemotherapy for malignant glioma (except polifeprosan 20 with carmustine implant)
At least 6 months since prior polifeprosan 20 with carmustine implant
At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
At least 2 weeks since prior vincristine or noncytotoxic chemotherapy
No concurrent chemotherapy

Endocrine therapy

Concurrent steroids allowed

Radiotherapy

See Disease Characteristics
At least 8 weeks since prior radiotherapy
No prior focal radiotherapy for malignant glioma (e.g., single-fraction stereotaxic radiotherapy or brachytherapy)
- Prior stereotactic radiosurgery boost as part of the initial fractionated external beam radiotherapy regimen allowed

Surgery

See Disease Characteristics

Other

Recovered from prior therapy
No prior investigational intracerebral agents
At least 4 weeks since prior systemic investigational agents
No prior localized antitumor therapy for malignant glioma
No concurrent anticoagulants or antiplatelet therapy, including, but not limited to, any of the following:
- Heparin
- Fractionated heparin
- Warfarin
- Aspirin
- Ticlopidine
- Clopidogrel
- Dipyridamole
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053040

Locations

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Investigator:

Nalin Gupta, MD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000269073, PBTC-011C, NEOPHARM-IL13PEI-151, NCI-5930
Study First Received:	January 27, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00053040 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood brain tumor

Study placed in the following topic categories:

Neuroectodermal Tumors
Brain Neoplasms
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Brain Tumor, Childhood
Glioma

Central Nervous System Neoplasms
Immunotoxins
Recurrence
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue

Nervous System Diseases
Glioma
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on July 02, 2009