A Molecular Biology And Phase II Study Of Lapatinib (GW572016) In Pediatric Patients With Recurrent Or Refractory Medulloblastoma, Malignant Glioma Or Ependymoma
I. Determine the inhibition of ERBB receptor signaling by lapatinib in pediatric patients
with recurrent or refractory medulloblastoma, primitive neuroectodermal tumors, high-grade
glioma, or ependymoma. (Molecular Biology) II. Determine the objective response rate
(complete response and partial response) in patients treated with this drug. (Phase II)
I. Determine the plasma pharmacokinetics and tumor tissue concentration of this drug in
these patients. (Molecular Biology and Phase II) II. Determine the effect of steroids on the
pharmacokinetics of this drug in these patients. (Phase II) III. Determine the incidence of
ERBB1, ERBB2, ERBB3, and ERBB4 expression and pathway activation in these patients. (Phase
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to
histology (medulloblastoma/primitive neuroectodermal tumor vs high-grade glioma vs
Molecular Biology Phase: Patients randomized to receive lapatinib prior to surgery receive
oral lapatinib twice daily for 7-14 days. Surgery is performed after 7-14 days of lapatinib
treatment. For patients randomized to not receive lapatinib, surgery is performed within 3
weeks of registration. After surgical resection, all molecular biology participants start
lapatinib treatment within 10 days post-surgery. The first dose of lapatinib post-surgery
initiates course 1. Patients receive oral lapatinib twice daily on days 1-28. Treatment
repeats every 28 days for up to 26 courses (2 years) in the absence of disease progression
or unacceptable toxicity.
Lapatinib Continuation/Phase II: Patients receive oral lapatinib twice daily on days 1-28.
Treatment repeats every 28 days for up to 26 courses (2 years) in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed for at least 30 days.
PROJECTED ACCRUAL: A total 84 patients will be accrued for this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Relative Phosphorylation of ERBB2 (Molecular Biology Objective)
Lapatinib may be able to control the growth of tumor cells. To assess the ability of lapatinib to block a molecule, the ERBB2 receptor, that signals tumor cells to divide, fresh frozen tissue from the surgical resection is processed by quantitative western blot analysis to assess the phosphorylation of ERBB2. The relative phosphorylation is a ratio of the phosphorylated ERBB2 measured in the tumor normalized to the level of total receptor protein and housekeeping protein. Lower values suggests more inhibition of the ERRB2 receptor signal and a decreased ability for tumor cell division.
7-14 days after starting therapy and prior to surgery
Maryam Fouladi, MD
Children's Hospital Medical Center, Cincinnati
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|