A Phase I/II Trial Of OSI-774 In Patients With Recurrent Malignant Gliomas And Malignant Gliomas Post Radiation Therapy
I. Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant
glioma or recurrent or progressive meningioma.
II. Determine the safety profile of this drug in these patients. III. Determine the
pharmacokinetics of this drug in these patients. IV. Determine the 6-month progression-free
survival, 12-month survival, and objective tumor response of patients treated with this
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
study phase (I vs II), concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no),
histology (recurrent GBM vs recurrent anaplastic glioma vs recurrent meningioma vs stable
GBM), preoperative candidacy (yes vs no), and concurrent steroids (yes vs no).
Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses
repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated
dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are
treated with erlotinib as above at the phase II dose. Patients not concurrently receiving
EIAEDs are treated with erlotinib as above at a predetermined dose.
Patients are followed for survival.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) or erlotinib hydrochloride defined as the dose at which fewer than one-third of patients experience DLT (phase I)
Summarized by descriptive statistics.
North American Brain Tumor Consortium
United States: Food and Drug Administration
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