A PHASE I STUDY OF COMBINED RADIATION RESPONSE MODIFIERS EMPLOYING HYDROXYUREA AND PENTOXIFYLLINE FOR TREATMENT OF GLIOBLASTOMA
OBJECTIVES: I. Determine the maximum tolerated dose of pentoxifylline administered with
hydroxyurea during a course of cranial radiotherapy in patients with glioblastoma
multiforme. II. Determine the toxicity of this regimen in these patients. III. Measure PTX
levels in plasma and CSF in order to assess whether therapeutic drug exposures (e.g.,
0.4-2.0 mM/24 hours) can be achieved with an acceptable level of toxicity. IV. Assess the
local control of glioblastoma in patients treated with this regimen. V. Determine the
response of surrounding normal brain in patients treated with this regimen. VI. Determine
the survival of patients treated with this regimen.
OUTLINE: This is a dose escalation study of pentoxifylline (PTX). Patients receive
hydroxyurea (HU) and PTX IV continuously 5 days a week concurrently with cranial
radiotherapy twice daily, 5 days a week, for 4 weeks in the absence of disease progression
or unacceptable toxicity. The first cohort of 3 patients is treated with radiotherapy and HU
alone. Subsequent cohorts of 3-6 patients receive HU and radiotherapy plus escalating doses
of PTX until the maximum tolerated dose of PTX is determined or serum or CSF drug
concentrations reach 0.4-2.0 mM in 6 consecutive patients with acceptable toxicity. The MTD
is defined as the dose immediately preceding that at which 2 of 6 patients experience
dose-limiting toxicity. Patients are followed at 1 week, at 1 and 3 months, every 3 months
for 2 years, and then every 4 months for 5 years.
PROJECTED ACCRUAL: A maximum of 24-34 patients will be accrued for this study.
Interventional
Primary Purpose: Treatment
Brian G. Fuller, MD
Study Chair
NCI - Radiation Oncology Branch; ROB
United States: Federal Government
CDR0000064077
NCT00019058
April 1995
Name | Location |
---|---|
Radiation Oncology Branch | Bethesda, Maryland 20892 |