Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma

Sponsor

INSYS Therapeutics Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00024570

Collaborator

(none)

Enrollment

Locations

79.9

Duration (Months)

7.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL3-PE38QQR is a protein that exhibits cell killing activity against a variety of IL13 receptor-positive tumor cell lines indicating that it may show a therapeutic benefit. In reciprocal competition experiments, the interaction between IL13-PE38QQR and the IL13 receptors was shown to be highly specific for human glioma cells.

IL13-PE38QQR will be infused in two courses of 96 hours each, eight weeks apart, directly into the malignant brain tumors of patients to determine the dose of drug these patients can tolerate. After that, the selected dose will be studied to give an estimate of the response rate, response duration, time to response, and survival after infusing that dose of IL13-PE38QQR into the recurrent malignant glioma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma Glioblastoma Multiforme Anaplastic Astrocytoma Mixed Oligoastrocytoma	Drug: IL13-PE38QQR Procedure: targeted fusion protein therapy Procedure: surgery	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the toxicities and maximum tolerated dose of IL13-PE38QQR delivered by continuous infusion into malignant glioma over 96 hours, in two courses eight weeks apart.
Estimate the response rate, response duration, time to response, and survival after interstitial infusion of IL13-PE38QQR into recurrent malignant glioma.
Describe the toxicities of interstitial infusion of IL13-PE38QQR at the selected dose.

PROTOCOL OUTLINE: Patients are expected to receive two IL13-PE38QQR infusions at 8-week intervals. For each course, drug will be infused through each of two catheters; infusion rate will be held constant during a 96-hour infusion.

In Phase I, the dose of IL13-PE38QQR will be increased by increasing the IL13-PE38QQR concentration in stepwise fashion, while holding infusion volume and duration constant. Three patients will be treated at each dose level until the maximum tolerated dose (MTD) is reached, and an additional three patients are treated at that level. In Phase II, patients will be treated at the selected MTD.

PROJECTED ACCRUAL: In Phase I, up to 30 patients will be treated. In Phase II, up to 35 patients will be treated.

Study Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study

Study Start Date :

Nov 1, 2000

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Disease Characteristics

Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma, glioblastoma multiforme and malignant mixed oligoastrocytoma. (Note: If diagnosis is dependent upon the Day 0 biopsy, pathology must be confirmed prior to start of IL13PE-38QQR infusion).
Must have received cranial radiotherapy, with tumor dose of at least 48 Gy, completed at least 12 weeks prior to study entry.
Must have radiographic evidence of recurrent or progressive supratentorial tumor compared with a previous study. The baseline tumor measurements must be determined within 2 weeks prior to study entry. The tumor must have a solid portion at least 1.0 cm but not more than 5.0 cm in maximum diameter. A maximum of one satellite lesion is permitted, if separated by less than 3 cm from the primary mass.
Stereotaxic biopsy at study entry must confirm the presence of glioma.

Patient Characteristics

Age 18 or greater.
Karnofsky Performance Score must be at least 60.
Hematologic status: Absolute neutrophils at least 1,500/mm^{3; Hemoglobin at least 10
gm/dL; Platelets at least 100,000/mm}3; PT & PTT less than or equal to the upper limit of normal.
Hepatic Status: Transaminases not more than 2.5 x upper limit of normal; Total Bilirubin not more than 2.0 mg/dL.
Must have recovered from toxicity of prior therapy; at least 6 weeks elapsed since receiving nitrosourea-containing chemotherapy and 3 weeks since receiving any other chemotherapy.
Must practice an effective method of birth control during the study.
Must understand the investigational nature of this study and its potential risks and benefits, and must sign informed consent.
No patients with more than two foci of tumor, tumor crossing the midline, or leptomeningeal tumor dissemination.
No patients with impending herniation, spinal cord compression, or uncontrolled seizures.
No patients who have received any localized antitumor therapy for the malignant glioma, either intralesional chemotherapy or focal radiotherapy (i.e. any form of stereotaxic RT or brachytherapy).
No patients who are receiving concurrent chemotherapy or another investigational agent.
No patients with prior or concurrent malignancy. (Patients with curatively treated carcinoma-in-situ or basal cell skin carcinoma OR who have been free of disease for at least 5 years are eligible).
Female patients must not be pregnant or breast-feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States
2	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
3	Emory University	Atlanta	Georgia	United States	30322
4	The Johns Hopkins University	Baltimore	Maryland	United States	21287
5	Henry Ford Health Systems	Detroit	Michigan	United States	48202
6	Wake Forest University	Winston-Salem	North Carolina	United States	27157
7	Cleveland Clinic	Cleveland	Ohio	United States	44195
8	University of Pennsylvania	Philadelphia	Pennsylvania	United States