Phase I Studies of TARCEVA™ (ERLOTINIB HYDROCHLORIDE, OSI-774) as Single Agent in Children With Refractory and Relapsed Malignant Brain Tumors and in Combination With Irradiation in Newly Diagnosed Brain Stem Glioma
- Establish the maximum tolerated dose of single-agent erlotinib hydrochloride in
pediatric patients with refractory or relapsed malignant brain tumors and in
combination with radiotherapy in pediatric patients with newly diagnosed brain stem
- Determine dose-limiting toxicities of these regimens.
- Define the safety profile of these regimens.
- Characterize the pharmacokinetic behavior of erlotinib hydrochloride in these patients.
- Evaluate the efficacy of these regimens.
- Correlate expression and mutations of epidermal growth factor receptor with treatment
OUTLINE: This is a multicenter, nonrandomized, open-label, dose-escalation study of
erlotinib hydrochloride. Patients are assigned to 1 of 2 treatment groups according to
- Group 1 (refractory or relapsed malignant brain tumors): Patients receive oral
erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the
absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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 (DLT).
- Group 2 (newly diagnosed brain stem glioma): Patients receive oral erlotinib
hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence
of unacceptable toxicity or disease progression. Beginning on day 1, patients also
undergo radiotherapy 5 days a week for 6 weeks .
Cohorts of 1-2 patients receive escalating doses of erlotinib hydrochloride until the MTD is
determined. The MTD is defined as the dose resulting in 25% of patients experiencing DLT at
Blood is collected for pharmacokinetic assessments and pharmacogenetic genotyping for
analysis of enzyme polymorphisms. Tumor tissue may be assessed for epidermal growth factor
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
Darren Hargrave, MD
Royal Marsden NHS Foundation Trust
United States: Federal Government