A Molecular Biology And Phase II Study Of Lapatinib (GW572016) In Pediatric Patients With Recurrent Or Refractory Medulloblastoma, Malignant Glioma Or Ependymoma
N/A
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
A Molecular Biology And Phase II Study Of Lapatinib (GW572016) In Pediatric Patients With Recurrent Or Refractory Medulloblastoma, Malignant Glioma Or Ependymoma
PRIMARY OBJECTIVES:
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)
SECONDARY OBJECTIVES:
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
II)
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.
PROJECTED ACCRUAL: A total 84 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Medulloblastoma/primitive neuroectodermal tumor
- High-grade glioma (anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma,
or anaplastic oligodendroglioma)
- Ependymoma
- Recurrent or refractory disease
- Measurable disease
PATIENT CHARACTERISTICS:
Age
- 21 and under
Performance status
- Karnofsky 50-100% (> 16 years of age) OR
- Lansky 50-100% (≤ 16 years of age)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3*
- Platelet count ≥ 100,000/mm^3*
- Hemoglobin ≥ 8.0 g/dL* NOTE: *Transfusion independent
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- ALT < 2.5 times ULN for age
- Albumin ≥ 2 g/dL
- No overt hepatic or biliary disease
Renal
- Creatinine ≤ 1.5 times ULN for age OR
- Glomerular filtration rate ≥ 70 mL/min
- No overt renal disease
Cardiovascular
- No overt cardiac disease
- Shortening fraction ≥ 27% by echocardiogram OR
- Ejection fraction ≥ 50% by gated radionuclide study
Pulmonary
- Pulse oximetry > 94%
- No dyspnea at rest
- No exercise intolerance
- No overt pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurological deficits allowed provided they remain stable ≥ 1 week before study entry
- Seizure disorders allowed provided symptoms are well controlled
- No uncontrolled infection
- No other significant medical illness not adequately controlled with appropriate
therapy or that would preclude study participation
- No other disease that would obscure toxicity or dangerously alter drug metabolism
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 1 week since prior nonmyelosuppressive anticancer biologic therapy
- At least 6 months since prior allogeneic bone marrow transplantation
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- At least 2 weeks since prior hematopoietic growth factors (filgrastim [G-CSF],
sargramostim [GM-CSF], or epoetin alfa)
Chemotherapy
- More than 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for
nitrosoureas or mitomycin) and recovered
Endocrine therapy
- Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week
before study entry
Radiotherapy
- At least 3 months since prior craniospinal irradiation (≥ 18 Gy)
- At least 4 weeks since prior local radiotherapy to primary tumor
- At least 2 weeks since prior focal irradiation to symptomatic metastatic sites
Surgery
- Not specified
Other
- At least 2 weeks since prior enzyme-inducing anticonvulsant drugs (EIACDs)
- At least 1 week since prior and no concurrent CYP3A4 inhibitors
- At least 6 months since prior amiodarone
- At least 2 weeks since prior and no concurrent CYP3A4 inducers
- At least 2 weeks since prior herbal or dietary supplements
- At least 2 days since prior and no concurrent cimetidine
- Concurrent ranitidine or omeprazole allowed only in conjunction with corticosteroids
given for increased intracranial pressure
- Concurrent antacids allowed provided they are administered > 1 hour before and > 1
hour after lapatinib administration
- No concurrent EIACDs
- No other concurrent anticancer or experimental agents or therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Relative Phosphorylation of ERBB2 (Molecular Biology Objective)
Outcome Description:
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.
Outcome Time Frame:
7-14 days after starting therapy and prior to surgery
Safety Issue:
No
Principal Investigator
Maryam Fouladi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital Medical Center, Cincinnati
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-03007
NCT ID:
NCT00095940
Start Date:
January 2005
Completion Date:
July 2010
Related Keywords:
- Brain and Central Nervous System Tumors
- recurrent childhood medulloblastoma
- recurrent childhood ependymoma
- childhood central nervous system germ cell tumor
- childhood choroid plexus tumor
- childhood craniopharyngioma
- childhood infratentorial ependymoma
- childhood grade III meningioma
- childhood oligodendroglioma
- childhood spinal cord neoplasm
- childhood supratentorial ependymoma
- childhood high-grade cerebral astrocytoma
- childhood low-grade cerebral astrocytoma
- recurrent childhood brain stem glioma
- recurrent childhood cerebellar astrocytoma
- recurrent childhood cerebral astrocytoma
- recurrent childhood supratentorial primitive neuroectodermal tumor
- recurrent childhood visual pathway and hypothalamic glioma
- Ependymoma
- Medulloblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| 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 |
