Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma
Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.
 Immunotoxin therapy may be an effective treatment for glioblastoma multiforme and anaplastic
 astrocytoma.

 PURPOSE: Phase I trial to study the effectiveness of immunotoxin therapy in treating children
 who have progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma
OBJECTIVES:

 -  Determine the maximum tolerated dose of intratumoral transferrin-CRM107 in pediatric
 patients with progressive or recurrent glioblastoma multiforme or anaplastic
 astrocytoma.

 -  Determine the safety of this drug in these patients.

 -  Determine the efficacy of this drug in these patients.

 -  Compare the efficacy of this drug in patients with different histological types of
 tumor, degrees of transferrin receptor expression, and serum antidiphtheria antibody
 titer levels.

 OUTLINE: This is a dose-escalation, open-label, multicenter study. Patients are assigned to 1
 of 2 treatment groups by age (5-9 vs 10-18).

 All patients undergo stereotactic radiosurgery for tumor biopsy and placement of 2
 intratumoral silastic infusion catheters pre-loaded with transferrin-CRM107 (Tf-CRM107).

 -  Group 1 (ages 5-9): Patients receive intratumoral Tf-CRM107 over 3-7 days via catheter.
 Treatment repeats after 6-10 weeks in the absence of unacceptable toxicity. Three
 cohorts of 3-6 patients receive escalating doses of Tf-CRM107 until the maximum
 tolerated dose (MTD) is determined.

 -  Group 2 (ages 10-18): Patients receive intratumoral Tf-CRM107 as in group 1. Two cohorts
 of 3-6 patients receive escalating doses of Tf-CRM107 until the MTD is determined.

 The MTD in both groups is defined as the dose preceding that at which 2 of 3 or 2 of 6
 patients experience dose-limiting toxicity.

 Patients are followed monthly for 6 months and then every 3 months for 6 months.

 PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed glioblastoma multiforme or anaplastic astrocytoma with the
 following tumor characteristics:

 -  Unifocal

 -  Unilateral and supratentorial

 -  Diameter no greater than 3.5 cm by contrast-enhanced MRI

 -  No more than 1 satellite tumor

 -  Recurrent or progressive disease

 -  Progressive disease defined as at least 25% increase in tumor volume by serial
 MRI or CT scans and/or at least 15% increase in the largest cross-sectional area
 of tumor as defined by the area of contrast agent enhancement

 -  Must have received prior conventional treatment comprising both of the following:

 -  Surgery (biopsy or debulking)

 -  Radiation therapy

 -  No evidence of mass effect on CT scan or MRI with more than a 5 mm midline shift
 and/or nausea, vomiting, reduced level of consciousness, or clinically significant
 papilledema

 PATIENT CHARACTERISTICS:

 Age

 -  5 to 18

 Performance status

 -  Karnofsky 60-100% OR

 -  Lansky Play 50-100%

 Life expectancy

 -  At least 3 months

 Hematopoietic

 -  Platelet count at least 100,000/mm^3

 -  Absolute neutrophil count at least 1,000/mm^3

 Hepatic

 -  Bilirubin no greater than 2.0 mg/dL

 -  AST and ALT no greater than 2.5 times the upper limit of normal (ULN)

 -  PT or aPTT no greater than 1.5 times ULN

 Renal

 -  Not specified

 Other

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for at least 2 months
 after study

 -  No acute viral, bacterial, or fungal infection requiring therapy

 -  Topical treatment for oral candidiasis allowed

 -  No other concurrent medical condition that would preclude anesthesia

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  No prior transferrin-CRM107

 Chemotherapy

 -  More than 1 month since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

 -  More than 3 months since prior biodegradable polymer wafers

 -  No concurrent chemotherapy

 Endocrine therapy

 -  Must be on stable dose of steroids for 7 days prior to infusion

 Radiotherapy

 -  See Disease Characteristics

 -  More than 3 months since prior radiotherapy

 -  More than 3 months since prior stereotactic radiosurgery

 -  More than 6 weeks since prior craniospinal irradiation

 -  No prior brachytherapy

 -  No concurrent radiotherapy

 Surgery

 -  See Disease Characteristics

 -  More than 1 month since prior surgery including tumor surgery or debulking

 -  No other concurrent surgery

 Other

 -  More than 30 days since prior investigational agents

 -  No other concurrent investigational therapy

 -  No other concurrent anti-cancer drugs