Lapatinib in Treating Young Patients With Recurrent or Refractory Central Nervous System Tumors
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|ClinicalTrials.gov Identifier: NCT00095940|
Recruitment Status : Completed
First Posted : November 9, 2004
Results First Posted : February 6, 2012
Last Update Posted : May 23, 2014
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: lapatinib ditosylate Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis Other: pharmacological study Procedure: positron emission tomography Procedure: magnetic resonance imaging||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Molecular Biology and Phase II Study of Lapatinib (GW572016) in Pediatric Patients With Recurrent or Refractory Medulloblastoma, Malignant Glioma or Ependymoma|
|Study Start Date :||October 2004|
|Actual Primary Completion Date :||July 2010|
|Actual Study Completion Date :||July 2010|
Experimental: Treatment (surgery, lapatinib)
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.
Drug: lapatinib ditosylate
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: pharmacological study
Other Name: pharmacological studies
Procedure: positron emission tomography
Procedure: magnetic resonance imaging
- Relative Phosphorylation of ERBB2 (Molecular Biology Objective) [ Time Frame: 7-14 days after starting therapy and prior to surgery ]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.
- Number of Participants With a Sustained Objective Response (Complete or Partial Response) (Phase II Objective) [ Time Frame: From start of therapy until the earliest of disease progression, death or end of the fourth course (recurrent medulloblastoma and recurrent high grade glioma) or end of the sixth course (recurrent ependymoma) ]A complete response is defined as complete disappearance of all tumor accompanied by a stable or improving neurologic exam, and a partial response is defined as 50% or more reduction in the tumor size by bi-dimensional measurement and a stable or improving neurologic exam. The response must be sustained for at least 8 weeks. The number of patients with a sustained objective response will be reported separately for each of the three disease groups.
- Tumor to Plasma Lapatinib Concentration (Molecular Biology Objective) [ Time Frame: First dose of lapatinib prior to surgery ]For participants randomized to receive lapatinib 7-14 days prior to surgery, plasma samples will be obtained with the first dose of lapatinib prior to surgery. The lapatinib concentration is measured in both the plasma samples and the tumor tissue obtained at surgery. Reported is the concentration of lapatinib observed in the tumor expressed as a percentage of the concentration observed in plasma.
- Maximum Concentration of Lapatinib in Plasma (Phase II Objective) [ Time Frame: First dose of lapatinib in course 1 ]Serial plasma samples for pharmacokinetic studies of lapatinib will be collected from consenting participants with the first dose of course 1.
- Number of Participants With Tumors Expressing Total ERBB2 [ Time Frame: Pre-treatment ]Total ERBB2 expression is assessed in participants enrolled in both the molecular biology trial and the phase II trial who provided pre-treatment formalin fixed paraffin embedded tumor material. The tumor material is analyzed by immunohistochemistry for expression of total ERBB2. Low, moderate, and intense expression are combined into one group vs. no total ERBB2 expression.
- Number of Participants With Tumors Expressing Phosphorylated ERBB2 (Phase II Objective) [ Time Frame: Pre-treatment ]Phosphorylated ERBB2 expression is assessed in patients who provided pre-treatment formalin fixed paraffin embedded tumor material. The tumor material is analyzed by immunohistochemistry for expression of phosphorylated ERBB2. Low, moderate, and intense expression are combined into one group vs. no phosphorylated ERBB2 expression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00095940
|United States, Tennessee|
|Pediatric Brain Tumor Consortium|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Maryam Fouladi||Pediatric Brain Tumor Consortium|