Clinical trial NCT00095940
Conditions: Recurrent Childhood Anaplastic Astrocytoma Recurrent Childhood Brain Stem Glioma Recurrent Childhood Ependymoma Recurrent Childhood Giant Cell Glioblastoma Recurrent Childhood Glioblastoma Recurrent Childhood Gliosarcoma Recurrent Childhood Medulloblastoma Recurrent Childhood Oligodendroglioma
Sponsor: National Cancer Institute (NCI)
Start date: 2004-10-01; Completion date: 2010-07-01
Enrollment: 52 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: 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.
Interventions: intervention 1: lapatinib ditosylate intervention 2: therapeutic conventional surgery intervention 3: laboratory biomarker analysis intervention 4: pharmacological study intervention 5: positron emission tomography intervention 6: magnetic resonance imaging
Intervention descriptions: intervention 1: Given orally intervention 2: Undergo surgery intervention 3: Correlative studies intervention 4: Correlative studies intervention 5: Correlative studies intervention 6: Correlative studies

Protocol documents: