Histologic Effect/Safety of Pre/Post-Operative IL13-PE38QQR in Recurrent Resectable Supratentorial Malignant Glioma Patients

NCT00024557 | Completed Phase 1

• 1 other identifier: IL13PEI-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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. Patients will receive IL13-PE38QQR via a catheter placed directly into the brain tumor. Tumor recurrence will be confirmed by biopsy. The next day, patients will start a continuous 48-hour infusion of IL13-PE38QQR into the tumor. The dose (concentration) will be increased in the pre-resection infusion until the endpoint is reached (histologic evidence of tumor cytotoxicity or a maximum tolerated dose). Tumor resection will be planned for one week after biopsy, plus or minus 1 day. A histologically-effective concentration (HEC) will be determined using pathologic observations. At the end of resection, three catheters will be placed in brain tissue next to the resection site and assessed within 24 hours using MRI. On the second day after surgery, IL13-PE38QQR infusion will begin and will continue for 4 days. The lowest pre-resection IL13-PE38QQR concentration will be used as the starting dose for post-resection infusions. After an HEC or maximum tolerated dose (MTD) is determined, the pre-resection infusion will no longer be administered. Subsequent patients will have tumor resection and placement of three peri-tumoral catheters at study entry. IL13-PE38QQR will be infused starting on the second day after surgery and continuing for 4 days. Escalation of the post-resection IL13-PE38QQR concentration will be continued until the previously-defined HEC or MTD is reached, after which duration of the post-resection infusion will be increased in one day increments for up to 6 days. If a post-resection MTD is obtained, there will be no increase in duration of infusion. In the final stage of the study, catheters will be placed 2 days after tumor resection, and a 4-day IL13-PE38QQR infusion will begin the day after catheter placement. Patients will be observed clinically and radiographically for toxicity and duration of tumor control.

Conditions

Malignant Glioma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Mixed Oligoastrocytoma; Malignant Astrocytoma

Keywords

neurosurgery, craniotomy; convection-enhanced delivery; CNS interstitial infusion; recombinant toxins; malignant glioma, recurrent; intratumoral therapy; positive pressure microinfusion

Interventions

IL13-PE38QQR DRUG

targeted fusion protein therapy PROCEDURE

surgery PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

-Disease Characteristics- Must have had prior histologically-confirmed diagnosis of supratentorial malignant glioma, grade 3 or 4, either on prior pathology or on biopsy at study entry, including anaplastic astrocytoma, glioblastoma multiforme, mixed oligoastrocytoma, or malignant astrocytoma NOS. Must have undergone prior surgical resection. Must have received cranial radiotherapy (RT), with tumor dose of at least 48 Gy, completed at least 4 weeks prior to study entry. Must have radiographic evidence of recurrent or progressive supratentorial tumor. If 12 weeks or less has elpased since external beam RT or localized RT (gamma-knife, brachytherapy), progression must be confirmed by metabolic imaging (MRS or PET). Tumor sample at study entry must confirm recurrent tumor. -Patient Characteristics- Age 18 or greater. Karnofsky Performance Score of at least 70. Hematologic status: Absolute neutrophils at least 1,500/mm\^3; Hemoglobin at least 9 gm/dL; Platelets at least 100,000/mm\^3. Coagulation Status: PT \& PTT less than or equal to the upper limit of normal. Must be candidate for re-operation. Must have recovered from toxicity of prior therapy; at least 6 weeks elapsed since receiving nitrosourea-containing chemotherapy, at least 4 weeks since receiving other cytotoxic therapy or an investigational agent, at least 2 weeks since receiving non-cytotoxic agents or vincristine. Must understand the investigational nature of this study and its potential risks and benefits, and sign informed consent. Must practice an effective method of birth control. No patients with signs of impending herniation, midline shift greater than 1 cm, uncontrolled seizures, or other neurologic conditions which would interfere with evaluation. No patients receiving any concurrent anti-tumor therapy (other than steroids). No patients with multifocal disease, or subependymal or leptomeningial tumor spread. No patients with metallic prosthesis that would prevent MRI and/or MRS scanning of the brain. Female patients must not be pregnant or breast-feeding.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• INSYS Therapeutics Inc: lead

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Recurrence

Interventions

IL13-PE38; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 20, 2001
• First Posted: September 21, 2001
• Study Start: June 1, 2001
• Primary Completion: June 1, 2006
• Study Completion: July 1, 2007
• Last Updated: June 6, 2011

Record last verified: 2011-06

Locations

US (4)