Trial Information

A Phase I Trial to Evaluate Repetitive Intravenous Doses of Gadolinium-Texaphyrin as a Radiosensitizer in Patients With Glioblastoma Multiforme

OBJECTIVES: I. Evaluate the toxic effects of gadolinium texaphyrin administered to patients
receiving cranial radiotherapy for glioblastoma multiforme. II. Determine the maximum
tolerated dose of this regimen in these patients. III. Determine the pharmacokinetic profile
of this regimen in these patients. IV. Determine the biodistribution of gadolinium
texaphyrin in both neoplastic tissue and normal brain parenchyma. V. Evaluate the effect and
accumulation of this regimen in normal brain parenchyma and neoplastic tissue by following
the change in enhancing volume and percent change in signal intensity over time.

OUTLINE: This is an open label, multicenter study. Arm I: Patients receive radiotherapy once
a day, 5 days a week, for 6 weeks. Gadolinium texaphyrin IV is administered every other day
within 2-5 hours prior to radiotherapy. Patients are evaluated at 1 month, and if no more
than 1 of 3 patients experiences unacceptable toxicity, 3 patients are entered on the
imaging portion of the study. Once arm I has successfully entered 3 patients with acceptable
toxicity profiles and 3 patients in the imaging portion of the study, patient enrollment
begins for arm II. Arm II: Cohorts of 3-9 patients receive radiotherapy as in arm I and
escalating doses of gadolinium texaphyrin IV administered within 2-5 hours prior to each
radiation dose. The maximum tolerated dose (MTD) of gadolinium texaphyrin is defined as the
dose at which no more than one third of the patients experience dose limiting toxicity. Arm
III: Patients experiencing dose limiting toxicity in arm II requiring dose reduction below
predetermined once a day limit receive gadolinium every other day, with radiotherapy as in
arm II. The MTD is defined as in arm II. Arm IV: An additional 3 patients are enrolled at
the MTD and enter the imaging portion of the study. Patients are followed for 1 month after
final radiation therapy.

PROJECTED ACCRUAL: At least 18 patients will be accrued for this study within 6 months.