Abstract

This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACTHYPOTHESISERBB signal inhibitors will have anti-tumor activity in a variety of pediatric brain tumors, including medulloblastomas/PNETs, high-grade gliomas, and ependymomas.
SPECIFIC AIMS Primary1. 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).2. To test the ability of lapatinib (GW572016) to inhibit ERBB receptor signaling in recurrent or refractory: medulloblastoma P/NET, high-grade glioma or ependymomas.3. To estimate the sustained objective response rates (CR plus PR) to lapatinib (GW572016) administered continuously at the MTD to childrenwith recurrent or refractory:medulloblastoma/PNET, high-grade glioma or ependymoma. Independent estimates of the ojbective response rates will be made for each of these three histologically defined strata.Secondary4. To characterize the plasma and tissue pharmacokinetics of lapatinib (GW5720196) in children.5. To assess the effect of steroids on the pharmacokinetics of lapatinib (GW572016).6. To explore the pharmacogenetic polmorphisms in lapatinib (GW572016) metabolizing enzymes and relate these polymorphisms to the drug pharmacokinetics.7. To estimate the incidence of ERBB1, ERBB2, ERBB3 and ERBB4 expression and pathway activation in recurent or refractory CNS tumors of childhood, including ependymoma, medulloblastoma/PNET and glioma.8. To identily additional genes both within and outside the canonical ERBB pathway that might act as determinants of response to lapatinib (GW572016)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000188-43
Application #
7605887
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-02-15
Project End
2007-11-30
Budget Start
2007-02-15
Budget End
2007-11-30
Support Year
43
Fiscal Year
2007
Total Cost
$2,636
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Hunsaker, Sanita L; Garland, Beth H; Rofey, Dana et al. (2018) A Multisite 2-Year Follow Up of Psychopathology Prevalence, Predictors, and Correlates Among Adolescents Who Did or Did Not Undergo Weight Loss Surgery. J Adolesc Health 63:142-150
Lanzieri, Tatiana M; Chung, Winnie; Leung, Jessica et al. (2018) Hearing Trajectory in Children with Congenital Cytomegalovirus Infection. Otolaryngol Head Neck Surg 158:736-744
Bollard, Catherine M; Tripic, Tamara; Cruz, Conrad Russell et al. (2018) Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. J Clin Oncol 36:1128-1139
Michalsky, Marc P; Inge, Thomas H; Jenkins, Todd M et al. (2018) Cardiovascular Risk Factors After Adolescent Bariatric Surgery. Pediatrics 141:
Lau, Chantal (2018) Breastfeeding Challenges and the Preterm Mother-Infant Dyad: A Conceptual Model. Breastfeed Med 13:8-17
Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P et al. (2017) Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. J Pediatr 190:100-107.e2
El-Hattab, Ayman W; Almannai, Mohammed; Scaglia, Fernando (2017) Arginine and citrulline for the treatment of MELAS syndrome. J Inborn Errors Metab Screen 5:
Lanzieri, Tatiana M; Chung, Winnie; Flores, Marily et al. (2017) Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics 139:
Thakur, Neeta; Barcelo, Nicolas E; Borrell, Luisa N et al. (2017) Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies. Chest 151:804-812
Gururangan, Sridharan; Reap, Elizabeth; Schmittling, Robert et al. (2017) Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11). Cancer Immunol Immunother 66:1589-1595

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