Clinical trial NCT00006268: Immunotoxin Therapy in Treating Patients With Malignant Glioma
Official title: Interstitial Infusion of IL 13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: National Institute of Neurological Disorders and Stroke
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Jon Weingart, MD
role: STUDY_CHAIR
References: