Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

Diffuse Intrinsic Pontine Glioma Clinical Trial

Official title:

Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01106794
• Other study ID #: DIPG-1
• Status: Recruiting
• Start date: April 2010
• Est. completion date: April 2030

Study information

• Verified date: February 2023
• Source: Children's National Research Institute
• Contact: Javad Nazarian, PhD
• Phone: 202-476-6022
• Email: JNazarian[@]cnmc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to prospectively collect specimens from pediatric patients with diffuse intrinsic pontine glioma or brainstem glioma, either during therapy or at autopsy, in order to characterize the molecular abnormalities of this tumor.

Description:

High grade diffuse intrinsic pontine glioma (DIPG) accounts for approximately 80% of pediatric brainstem tumors and 10% of pediatric brain tumors, and is the most lethal form of brainstem gliomas in children. There is currently no effective therapy to treat these tumors. We hypothesize that this tumor exhibits unique molecular abnormalities leading to altered RNA and protein expression. The aim of this trial is to collect specimens from pediatric patients with diffuse intrinsic pontine glioma including serum, cerebrospinal fluid, urine, brain tumor and other constitutional tissue, during therapy and/or at autopsy. Our goal is to study this tissue to characterize the genetic abnormalities that lead to tumor formation in order to identify key molecules as biomarkers which we can target to design and test new and more effective treatments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 2030
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Patients of any age with clinical and radiologic diagnosis of diffuse intrinsic pontine glioma

• Patients with other high-grade gliomas originating in the brainstem

• Patients with focal gliomas (WHO grade I/II) of the brainstem

Exclusion Criteria:

• Patients with any type of infiltrative low grade (WHO grade I and II) or high grade glioma (WHO grade III and IV) originating outside the brainstem

• Patients harboring primary brainstem tumors with other histologic diagnoses (e.g., PNET)

Related Conditions & MeSH terms

• Brainstem Glioma
• Diffuse Intrinsic Pontine Glioma
• Glioma

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's National Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (11)

Ahsan S, Raabe EH, Haffner MC, Vaghasia A, Warren KE, Quezado M, Ballester LY, Nazarian J, Eberhart CG, Rodriguez FJ. Increased 5-hydroxymethylcytosine and decreased 5-methylcytosine are indicators of global epigenetic dysregulation in diffuse intrinsic p — View Citation

Ballester LY, Wang Z, Shandilya S, Miettinen M, Burger PC, Eberhart CG, Rodriguez FJ, Raabe E, Nazarian J, Warren K, Quezado MM. Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol. 2013 Sep;3 — View Citation

Becher OJ, Hambardzumyan D, Walker TR, Helmy K, Nazarian J, Albrecht S, Hiner RL, Gall S, Huse JT, Jabado N, MacDonald TJ, Holland EC. Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma. Cancer Res. 2010 Mar 15;70(6):2548-57. doi: 10.1158/0008-5472.CAN-09-2503. Epub 2010 Mar 2. — View Citation

Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tab — View Citation

Kambhampati M, Panditharatna E, Yadavilli S, Saoud K, Lee S, Eze A, Almira-Suarez MI, Hancock L, Bonner ER, Gittens J, Stampar M, Gaonkar K, Resnick AC, Kline C, Ho CY, Waanders AJ, Georgescu MM, Rance NE, Kim Y, Johnson C, Rood BR, Kilburn LB, Hwang EI, Mueller S, Packer RJ, Bornhorst M, Nazarian J. Harmonization of postmortem donations for pediatric brain tumors and molecular characterization of diffuse midline gliomas. Sci Rep. 2020 Jul 2;10(1):10954. doi: 10.1038/s41598-020-67764-2. — View Citation

Kambhampati M, Perez JP, Yadavilli S, Saratsis AM, Hill AD, Ho CY, Panditharatna E, Markel M, Packer RJ, Nazarian J. A standardized autopsy procurement allows for the comprehensive study of DIPG biology. Oncotarget. 2015 May 20;6(14):12740-7. doi: 10.18632/oncotarget.3374. — View Citation

Nikbakht H, Panditharatna E, Mikael LG, Li R, Gayden T, Osmond M, Ho CY, Kambhampati M, Hwang EI, Faury D, Siu A, Papillon-Cavanagh S, Bechet D, Ligon KL, Ellezam B, Ingram WJ, Stinson C, Moore AS, Warren KE, Karamchandani J, Packer RJ, Jabado N, Majewski — View Citation

Panditharatna E, Yaeger K, Kilburn LB, Packer RJ, Nazarian J. Clinicopathology of diffuse intrinsic pontine glioma and its redefined genomic and epigenomic landscape. Cancer Genet. 2015 Jul-Aug;208(7-8):367-73. doi: 10.1016/j.cancergen.2015.04.008. Epub 2015 May 1. — View Citation

Saratsis AM, Kambhampati M, Snyder K, Yadavilli S, Devaney JM, Harmon B, Hall J, Raabe EH, An P, Weingart M, Rood BR, Magge SN, MacDonald TJ, Packer RJ, Nazarian J. Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine gli — View Citation

Saratsis AM, Yadavilli S, Magge S, Rood BR, Perez J, Hill DA, Hwang E, Kilburn L, Packer RJ, Nazarian J. Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid. Neuro Oncol. 2012 May;14(5):547-60. doi: 1 — View Citation

Yadavilli S, Scafidi J, Becher OJ, Saratsis AM, Hiner RL, Kambhampati M, Mariarita S, MacDonald TJ, Codispoti KE, Magge SN, Jaiswal JK, Packer RJ, Nazarian J. The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma. Oncotarget. 2015 May 20;6(14):12141-55. doi: 10.18632/oncotarget.3716. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling	Collected tumor and normal samples will potentially be used for RNA genome-wide expression pattern profiling.	5 years
Primary	Validation of results of the genome-wide analysis	The molecular analysis done on collected samples will be validated through whole genome sequencing.	5 years
Primary	Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid	To obtain full characterization of collected samples, proteomic profiling will be done on tumor and normal samples collected.	5 years
Primary	Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue	Collected tumor and normal samples will have the immunochemistry and western blot compared to assess protein expression variation.	5 years
Primary	Genome-wide analysis of tumor samples and normal brainstem tissue	To obtain full characterization of collected samples, whole genome sequencing will be done on tumor and normal samples collected.	5 years
Primary	In vitro and in vivo molecular analysis of collected samples	Collected samples will potentially be used for in vitro analysis and generation of animal models of this tumor.	5 years
Secondary	Assess aspects associated with specimen acquisition, including potential benefits and drawbacks	In an effort to continue to draw knowledge from samples collected, potential benefits and drawbacks from specimen acquisition will be continuously accessed.	5 years

External Links

•   Children's National Medical Center