Interstitial Infusion of IL 13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Interstitial Infusion of IL 13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Jon Weingart, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000068211
NCT ID:
NCT00006268
Start Date:
October 2000
Completion Date:
March 2005
Related Keywords:
- Brain and Central Nervous System Tumors
- recurrent adult brain tumor
- adult glioblastoma
- adult anaplastic astrocytoma
- adult mixed glioma
- adult giant cell glioblastoma
- adult gliosarcoma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham, Alabama 35294-3300 |
| Comprehensive Cancer Center at Wake Forest University | Winston-Salem, North Carolina 27157-1082 |
| Abramson Cancer Center at the University of Pennsylvania | Philadelphia, Pennsylvania 19104 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Josephine Ford Cancer Center at Henry Ford Health System | Detroit, Michigan 48202 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa, Florida 33612 |
| National Institute of Neurological Disorders and Stroke | Bethesda, Maryland 20892-1414 |
