Immunotoxin Therapy in Treating Children With Recurrent Malignant Gliomas

NCT00053040 | Withdrawn Phase 1 DMC

• 4 other identifiers: CDR0000269073PBTC-011CNEOPHARM-IL13PEI-151NCI-5930
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent childhood brain tumor

Outcome Measures

Primary Outcomes (4)

• Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)

  Toxicities reported are those occurring from the start of the IL13 infusion after catheter placement to Day 35 (30 days after the end of the infusion) if there are no or mild MRI changes on Day 35 around the catheter tract or tip. If the MRI change on Day 35 indicates moderate or extensive changes around the catheter tract or tip then the toxicities reported are those occurring from the start of the IL13 infusion to Day 75 (70 days after the end of the infusion).

  Start of IL13-PE38QQR infusion to Day 35 or Day 75

• Maximum safe flow rate (Phase I)

  Two total flow rates of IL13-PE38QQR, 500 uL/hr and 750 uL/hr, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum safe flow rate. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.

  Start of IL13-PE38QQR infusion to Day 35 or Day 70

• Maximum tolerated infusion concentration (Phase I)

  Two infusion concentrations of IL13-PE38QQR, .25 ug/mL and .50 ug/mL, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum tolerated infusion concentration. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.

  Start of IL13-PE38QQR infusion to Day 35 or Day 70

• Survival post initial recurrence or progression at the maximum safe total flow rate and maximum tolerated infusion concentration (Phase II)

  Initial progression to date of death from any cause

Secondary Outcomes (4)

• Progression-free survival (Phase II)

  Initial progression to second progression

• IL13receptor α2 chain expression status and distribution

  Pre-treatment

• Overall safety

  Start of IL13-PE38QQR infusion to disease progression or alternative treatment

• Tolerability

  Start of IL13-PE38QQR infusion to disease progression or alternative treatment

Study Arms (1)

Surgery for tumor resection + IL13-PE38QQR infusion

EXPERIMENTAL

Biological: cintredekin besudotox; Procedure: conventional surgery

Interventions

cintredekin besudotox BIOLOGICAL

IL13-PE38QQR is administered intracerebrally by continuous convection enhanced infusion at a starting concentration of 0.25 μg/mL. Infusion duration will be held constant at 96 hours (4 days). The phase I component of this study is to estimate the maximum safe total flow rate and the maximum safe infusion concentration.

Also known as: IL13-PE38QQR

Surgery for tumor resection + IL13-PE38QQR infusion

conventional surgery PROCEDURE

Conventional surgery is used for tumor resection prior to catheter placement for IL13-PE38QQR infusion.

Surgery for tumor resection + IL13-PE38QQR infusion

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

IL13-PE38

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Anuradha Banerjee, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: January 27, 2003
• First Posted: January 28, 2003
• Study Start: October 1, 2005
• Last Updated: September 24, 2010

Record last verified: 2010-09