Radiation Therapy and Gadolinium Texaphyrin in Treating Patients With Supratentorial Glioblastoma Multiforme

PHASE I TRIAL OF GADOLINIUM TEXAPHYRIN (PCI -0120) AS A RADIOSENSITIZER DURING STEREOTACTIC RADIOSURGERY BOOST FOR GLIOBLASTOMA MULTIFORME

Phase I trial to study the effectiveness of radiation therapy and gadolinium texaphyrin in treating patients who have supratentorial glioblastoma multiforme. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy.

PRIMARY OBJECTIVES:

I. Determine the frequency and grade of toxicity of gadolinium texaphyrin as a radiosensitizer at two dose levels in patients with supratentorial glioblastoma multiforme undergoing stereotactic radiosurgery.

II. Compare the tumor, normal brain, and plasma concentrations of this drug regimen to 1.5 and 8 Tesla MRI images in this patient population.

III. Determine if the 8 Tesla images provide more data than the 1.5 Tesla images in terms of the radiosensitizing drug distribution in the tumor in these patients.

OUTLINE: This is a dose escalation study.

Within 5 weeks following surgery, patients receive daily external beam radiotherapy five days a week for 5 weeks. Within 2 weeks following completion of radiotherapy, patients receive gadolinium texaphyrin IV over 2 hours followed 3 hours later by stereotactic radiosurgery. Patients undergoing surgical debulking of tumor prior to external beam radiotherapy receive gadolinium texaphyrin IV over 2 hours, 3 hours prior to surgery in addition to the dose prior to stereotactic radiosurgery.

Cohorts of 3-6 patients receive escalating doses of gadolinium texaphyrin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.

Patients are followed monthly for 3 months, and then every 3 months for 5 years or until death.

PROJECTED ACCRUAL: Approximately 12-18 patients will be accrued for this study within 12-18 months.

Inclusion Criteria:

• Histologically confirmed supratentorial glioblastoma multiforme by stereotactic biopsy, open biopsy, or resection
• Maximum diameter of the tumor mass must be no greater than 4 cm in any dimension, including following debulking surgery
• Tumor must be at least 1.0 cm from the optic chiasm and brainstem
• No oligodendrogliomas, meningiomas, or grade I, II, or III astrocytomas
• No infratentorial tumors
• No multifocal glioblastoma multiforme
• Tumor enhances on MRI
• Must have visible tumor on postoperative MRI following surgical resection
• Performance status - Karnofsky 60-100%
• At least 3 months
• Hemoglobin at least 10.0 g/dL
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• SGPT no greater than 60 U/L
• Creatinine no greater than 1.3 mg/dL
• Blood urea nitrogen no greater than 24 mg/dL
• Neurological function status 0-3
• No evidence of neuropathy
• No glucose-6-phosphate dehydrogenase deficiency
• No known history of porphyria
• History of prior malignancies allowed
• HIV positive status allowed
• No medical contraindication to MRI imaging (i.e., pacemaker, aneurysm clip, or nonsecure metal fragment close to a critical structure)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to and during study
• At least 6 weeks since prior chemotherapy
• Concurrent steroids allowed
• No prior radiotherapy to the brain or upper neck
• No greater than 5 weeks since prior surgery and recovered