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


Phase 1/Phase 2
3 Years
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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


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)

- Estimate the rate of survival after initial progression in patients treated at the
maximum safe flow rate and MTiC with this drug. (Phase II)

Secondary

- Describe the overall safety and tolerability of this regimen in these patients from the
start of infusion through disease progression or initiation of alternative treatment.

- Determine the IL13 receptor α2 chain expression status and distribution in pediatric
recurrent or progressive malignant gliomas

- Estimate 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 at the maximum safe 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 maximum safe flow rate and MTiC
determined in the phase I of the study.

Patients are followed at week 18 after catheter placement and then every 8 weeks thereafter
until death, disease progression, or completion of six months (phase I) or 12 months (phase
II) of follow-up after the end of IL13-PE38QQR infusion. Phase II patients who complete one
year of follow-up without disease progression are followed every 12 weeks thereafter until
death.

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

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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).

Outcome Time Frame:

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

Safety Issue:

Yes

Principal Investigator

Anuradha Banerjee, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000269073

NCT ID:

NCT00053040

Start Date:

October 2005

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent childhood brain tumor
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Glioma

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