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

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

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma Multiforme
• Intervention / Treatment: Drug: TP-38; Drug: TP38

• Study Type: Interventional
• Enrollment (Actual): 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 (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 amenorrhoeic for at least 12 months to be considered of 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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TP38 50 ng/mL	Drug: TP-38; Recombinant chimeric protein; Other Names: immunotoxin
Experimental: TP38 100 ng/mL	Drug: TP38; recombinant chimeric protein; Other Names: immunotoxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	% patients alive	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression (TTP)	An independent review committee will review MRI scans and will be blinded to the dose each patient received.	28 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: October 28, 2003
• First Submitted That Met QC Criteria: October 28, 2003
• First Posted (Estimate): October 29, 2003

Study Record Updates

• Last Update Posted (Estimate): January 20, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: gross total resection
• 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; Physiological Effects of Drugs; Immunologic Factors; Immunotoxins
• Other Study ID Numbers: IXR-102-22-188

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No