Know Cancer

or
forgot password

A Molecular Biology And Phase II Study Of Lapatinib (GW572016) In Pediatric Patients With Recurrent Or Refractory Medulloblastoma, Malignant Glioma Or Ependymoma


Phase 2
N/A
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

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 PhiladelphiaPhiladelphia, Pennsylvania  19104
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Texas Children's Cancer Center and Hematology Service at Texas Children's HospitalHouston, Texas  77030-2399