Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma

Xenova Biomedix

Status and phase: Unknown; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Biological: transferrin-CRM107

Study type: Interventional

Funder types: Industry

Identifiers

NCT00052624

KSB-311P/CI/001

CDR0000258574 (Registry Identifier)

MUSC-10550

Details and patient eligibility

About

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

Full description

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.

Sex: All

Ages: 5 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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