Safety and Efficacy Study to Treat Recurrent Grade 4 Malignant Brain Tumors

A Multicenter Phase II Study of TP-38 in Those Patients With Glioblastoma Multiforme Who Have Recurred or Progressed After Previous Resection and Radiation Therapy and Are Scheduled for Gross Total Resection

Immunotoxin therapy may be effective in treating malignant glioma. Immunotoxins can locate tumor cells and kill them without harming normal cells.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: TP-38

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The patients must fulfill all the following criteria:

• Previous histologically-confirmed diagnosis of primary GBM (glioblastoma multiforme, glioma grade 4 at time of first diagnosis).
• Histologically-confirmed and MRI diagnosed recurrent or progressive GBM after previous resection (surgical or biopsy) and radiation therapy.
• Medically capable of undergoing the planned surgical gross total resection and the catheter placement.
• Age ≥ 18.
• Karnofsky Performance Status of ≥ 70%.
• Life expectancy of ≥ 3 months.
• Patients must already be taking or begin taking corticosteroids at a stable dose of 4 mg every 6 hours for at least 72 hours prior to catheter placement.
• Patients must be capable of taking, or already taking, anticonvulsant medication.
• Patients must have read, signed, and dated an informed consent according to ICH-GCP, the local regulatory requirement and the rules followed at each institution.

Exclusion Criteria:

Patients fulfilling any of the following criteria should not be enrolled in the study:

• Previous myelosuppressive chemotherapy within the past 4 weeks of the start of the infusion. Patients who have received more than two chemotherapy regimens (single therapy or combination therapy) are ineligible.
• Any form of brain radiation within 10 weeks of the start of the infusion.
• Previous gamma knife radiosurgery, stereotactic radiosurgery, and/or internal radiotherapy, unless the recurrence/progression is histologically confirmed (fine-needle biopsy).
• Prior intracavitary biologic response modifiers or monoclonal antibodies.
• Uncontrolled seizures.
• Bilateral or multifocal tumors.
• Evidence of cerebral uncal herniation.
• Midline brain shift on MRI scan of > 0.5 cm prior to resection; patients with subfalcine herniation may be enrolled.
• Tumors involving the brainstem or cerebellum.
• Diffuse subependymal or CSF disease.
• Women who are pregnant or breast feeding. All women of child-bearing potential should be excluded unless they have a negative pregnancy test and are using adequate contraceptive measures or are surgically sterile. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-childbearing.
• Fertile males not practicing adequate contraception and whose female partners are not using adequate contraceptive protection.
• Prior or concurrent investigational treatment within 30 days of study entry.
• Active infection requiring treatment or having an unexplained febrile illness.
• Systemic diseases or other conditions which may be associated with unacceptable anesthetic/operative risk and/or which would not allow safe completion of this study protocol.
• Prior or concurrent malignancy (curatively treated carcinoma-in-situ or basal cell carcinoma or patients who have been disease free for at least 5 years are eligible).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 40 mL of TP-38 at a 100 nanograms/mL concentration	Drug: TP-38; TP-38 is a recombinant chimeric protein composed of the epidermal growth factor (EGFR) binding ligand (TGF-α)and a genetically engineered form of the Pseudomonas exotoxin, PE-38.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate TP-38 at a 100 nanograms/mL concentration for sufficient activity	26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy parameters including time to progression, safety, and survival	26 weeks

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: February 22, 2005
• First Submitted That Met QC Criteria: February 22, 2005
• First Posted (Estimate): February 23, 2005

Study Record Updates

• Last Update Posted (Estimate): May 23, 2011
• Last Update Submitted That Met QC Criteria: May 20, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Recurrent Glioblastoma Multiforme; Gross Total Resection; Convection Enhanced Delivery
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: IXR-202-22-188