Recurrent Childhood Ependymoma Clinical Trial
Official title:
Molecular Biology and Phase II Study of Lapatinib (GW572016) in Pediatric Patients With Recurrent or Refractory Medulloblastoma, Malignant Glioma or Ependymoma
This phase I/II trial studies lapatinib to see how well it works in treating young patients with recurrent or refractory central nervous system (CNS) tumors. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
PRIMARY OBJECTIVES:
I. To estimate the MTD and describe the DLT of oral lapatinib (GW572016) administered twice
daily for 28 days to children with recurrent or refractory malignant brain tumors who are
not receiving steroids (Stratum 1) and to describe toxicities in those who are receiving
steroids (Stratum 2).
II. To test the ability of lapatinib (GW572016) to inhibit ERBB receptor signaling in
recurrent or refractory: medulloblastoma/PNET, high-grade glioma or ependymomas.
III. To estimate the sustained objective response rates (CR plus PR sustained for 8 weeks)
to lapatinib (GW572016) administered continuously at the MTD (900 mg/m2/dose bid) to
children with recurrent or refractory: medulloblastoma/PNET, high-grade glioma or
ependymoma.
SECONDARY OBJECTIVES:
I. To characterize the plasma pharmacokinetics of lapatinib (GW572016) and tumor tissue
lapatinib (GW572016) concentration in children.
II. To assess the effect of steroids on the pharmacokinetics of lapatinib (GW572016).
III. To explore the pharmacogenetic polymorphisms in lapatinib (GW572016) metabolizing
enzymes and relate these polymorphisms to the drug pharmacokinetics.
IV. To estimate the incidence of ERBB1, ERBB2, ERBB3 and ERBB4 expression and pathway
activation in recurrent or refractory CNS tumors of childhood, including ependymoma,
medulloblastoma/PNET and glioma.
V. To identify additional genes both within and outside the canonical ERBB pathway that
might act as determinants of response to lapatinib (GW572016).
VI. To explore changes in PET and correlative magnetic resonance imaging in children
receiving lapatinib. Imaging studies may be combined across similar PBTC protocols to
increase the power for detecting correlations among scans and associations with outcome.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to
histology (medulloblastoma/primitive neuroectodermal tumor vs high-grade glioma vs
ependymoma).
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.
;
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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