A Phase I/II Trial of a New Tyrosine Kinase Inhibitor (Tarceva; Erlotinib Hydrochloride; OSI-774) During and After Radiotherapy in the Treatment of Patients With Newly Diagnosed High Grade Glioma and Unfavorable Low-Grade Glioma
- Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when
administered during and after radiotherapy in young patients with newly diagnosed
high-grade glioma and unfavorable low-grade glioma.
- Determine the 1- and 2-year progression-free survival of patients treated with this
- Determine the toxic effects of this regimen in these patients.
- Correlate genetic abnormalities in epidermal growth factor receptor (EGFR) and
components of downstream pathways with treatment response in patients treated with this
- Determine the ability of erlotinib to inhibit EGFR signaling in patients with
high-grade glioma who require second surgery.
- Determine the pharmacokinetics of erlotinib and its metabolites in these patients.
- Correlate plasma and cerebrospinal fluid levels of vascular endothelial growth factor
and basic fibroblast growth factor with tumor response in patients treated with this
- Correlate irradiation dosimetry with patterns of failure, standard and investigational
imaging, and toxicity in patients treated with this regimen.
OUTLINE: This is a phase I dose-escalation study of erlotinib followed by a phase II study.
- Phase I: Patients undergo radiotherapy once daily, 5 days week, for approximately 6½
weeks. Beginning on the first day of radiotherapy, patients receive oral erlotinib once
daily for up to 2 years.
Cohorts of patients receive escalating doses of erlotinib until the maximum tolerated dose
(MTD) is determined.
- Phase II: Patients will receive erlotinib as in phase I at the MTD and undergo
radiotherapy as in phase I.
PROJECTED ACCRUAL: A total of 75-80 patients (15-20 for the phase I portion and 60 for the
phase II portion) will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
estimate the MTD and determine the DLT of erlotinib during and after RT in children, adolescents, and young adults with newly diagnosed high-grade glioma and unfavorable low-grade glioma
Alberto Broniscer, MD
St. Jude Children's Research Hospital
United States: Food and Drug Administration
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|University of California San Diego||La Jolla, California 92093|
|Duke Children's Hospital and Health Center||Durham, North Carolina 27710|