Immunotoxin Therapy in Treating Patients With Malignant Glioma

New Approaches to Brain Tumor Therapy Consortium

Status and phase: Completed; Phase 2; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: isolated perfusion; Biological: cintredekin besudotox; Procedure: conventional surgery

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006268

NABTT-9903

JHOC-NABTT-9903

CDR0000068211

NEOPHARM-TS-G1-TI4

NEOPHARM-IL13PEI-001-R03

Details and patient eligibility

About

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for malignant glioma.

PURPOSE: Phase I/II trial to study the effectiveness of immunotoxin therapy in treating patients who have malignant glioma.

Full description

OBJECTIVES:

• Determine the toxic effects and maximum tolerated dose (MTD) of interstitial interleukin-13 PE38QQR immunotoxin in patients with malignant glioma.
• Determine the response rate, duration of response, time to response, overall survival, and time to progression in patients treated with this regimen.
• Determine the toxic effects of this drug at the MTD in these patients.

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

Patients undergo stereotactic biopsy of brain tumor followed by CT guided stereotactic placement of 2 intratumoral catheters on day 0. Patients with histologically confirmed malignant glioma receive interleukin-13 PE38QQR immunotoxin interstitially over 96 hours beginning on day 1. Patients with a residual enhancing mass undergo repeat catheter placement on day 56 and then receive a second interstitial infusion beginning on day 57 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-13 PE38QQR immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for phase I of the study within 6 months and a total of 12-35 patients will be accrued for phase II of the study within 10-12 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven malignant glioma (grade 3 or 4)

  • Anaplastic astrocytoma
  • Glioblastoma multiforme
  • Malignant mixed oligoastrocytoma

• Must have undergone cranial radiotherapy with tumor dose of at least 48 Gy and at least 12 weeks prior to study

• Must have undergone supratentorial brain tumor surgery or biopsy

• Must have radiographic evidence of recurrent or progressive supratentorial tumor compared with prior study

  • Must have solid portion measuring 1.0-5.0 cm in maximum diameter
  • Maximum of 1 satellite lesion allowed if separated from the primary mass by less than 3 cm
  • No tumor crossing the midline
  • No leptomeningeal tumor dissemination
  • No impending herniation or spinal cord compression

• No uncontrolled seizures

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

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

Hepatic:

• PT and PTT no greater than upper limit of normal (ULN)
• SGOT and SGPT no greater than 2.5 times ULN
• Bilirubin no greater than 2.0 mg/dL

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior intralesional chemotherapy for malignant glioma
• At least 3 weeks since other prior chemotherapy (6 weeks since prior nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed, but dose must remain stable or be tapered during study

Radiotherapy:

• See Disease Characteristics
• No prior focal radiotherapy (e.g., any form of stereotactic radiotherapy or brachytherapy) for malignant glioma

Surgery:

• See Disease Characteristics

Other:

• Recovered from any prior therapy
• No other concurrent investigational agent