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

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ClinicalTrials.gov Identifier: NCT01106794

Recruitment Status : Recruiting

First Posted : April 20, 2010

Last Update Posted : February 10, 2023

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Sponsor:

Information provided by (Responsible Party):

Javad Nazarian, Children's National Research Institute

Study Description

Brief 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.

Condition or disease
Diffuse Intrinsic Pontine Glioma Brainstem Glioma

Detailed 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.

Study Design

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Study Type :	Observational
Estimated Enrollment :	100 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
Actual Study Start Date :	April 2010
Estimated Primary Completion Date :	April 2025
Estimated Study Completion Date :	April 2030

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Glioma Childhood Brain Stem Glioma Diffuse Intrinsic Pontine Glioma Neuroepithelioma

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Patient samples Fresh-frozen and fixed tumor samples, correspondent normal brain tissue samples, cerebrospinal fluid, urine, and serum samples from patients affected with diffuse intrinsic pontine glioma or brainstem glioma

Outcome Measures

Primary Outcome Measures :

Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling [ Time Frame: 5 years ]
Collected tumor and normal samples will potentially be used for RNA genome-wide expression pattern profiling.
Validation of results of the genome-wide analysis [ Time Frame: 5 years ]
The molecular analysis done on collected samples will be validated through whole genome sequencing.
Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid [ Time Frame: 5 years ]
To obtain full characterization of collected samples, proteomic profiling will be done on tumor and normal samples collected.
Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue [ Time Frame: 5 years ]
Collected tumor and normal samples will have the immunochemistry and western blot compared to assess protein expression variation.
Genome-wide analysis of tumor samples and normal brainstem tissue [ Time Frame: 5 years ]
To obtain full characterization of collected samples, whole genome sequencing will be done on tumor and normal samples collected.
In vitro and in vivo molecular analysis of collected samples [ Time Frame: 5 years ]
Collected samples will potentially be used for in vitro analysis and generation of animal models of this tumor.

Secondary Outcome Measures :

Assess aspects associated with specimen acquisition, including potential benefits and drawbacks [ Time Frame: 5 years ]
In an effort to continue to draw knowledge from samples collected, potential benefits and drawbacks from specimen acquisition will be continuously accessed.

Biospecimen Retention: Samples With DNA

Cerebrospinal fluid, serum, urine, brainstem tumor and constitutional tissue from patients with diffuse intrinsic pontine glioma or brainstem glioma will be collected.

Eligibility Criteria

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Community sample

Criteria

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)

Contacts and Locations

Information from the National Library of Medicine

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): NCT01106794

Contacts

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Contact: Javad Nazarian, PhD	202-476-6022	JNazarian@cnmc.org
Contact: Madhuri Kambhampati, MS	202-476-5198	mkambhampati@childrensnational.org

Locations

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United States, District of Columbia
Children's National Medical Center	Recruiting
Washington, District of Columbia, United States, 20010
Principal Investigator: Javad Nazarian, PhD
Sub-Investigator: Roger Packer, MD
Sub-Investigator: Suresh Magge, MD
Sub-Investigator: Amanda L Muhs, MD

Sponsors and Collaborators

Children's National Research Institute

Investigators

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Principal Investigator:	Javad Nazarian, PhD	Children's National Research Institute

More Information

Additional Information:

Children's National Medical Center This link exits the ClinicalTrials.gov site

Publications of Results:

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;37(9):1357-64. doi: 10.1097/PAS.0b013e318294e817.

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: 10.1093/neuonc/nos067. Epub 2012 Apr 5.

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 pontine glioma. Acta Neuropathol Commun. 2014 Jun 3;2:59. doi: 10.1186/2051-5960-2-59.

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, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet. 2014 May;46(5):451-6. doi: 10.1038/ng.2936. Epub 2014 Apr 6.

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 glioma reveals distinct molecular subtypes. Acta Neuropathol. 2014;127(6):881-95. doi: 10.1007/s00401-013-1218-2. Epub 2013 Dec 3. Erratum In: Acta Neuropathol. 2020 Aug;140(2):247.

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 J, Nazarian J. Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma. Nat Commun. 2016 Apr 6;7:11185. doi: 10.1038/ncomms11185.

Other Publications:

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.

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.

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.

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.

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.

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Responsible Party:	Javad Nazarian, Associate Professor, Children's National Research Institute
ClinicalTrials.gov Identifier:	NCT01106794
Other Study ID Numbers:	DIPG-1
First Posted:	April 20, 2010 Key Record Dates
Last Update Posted:	February 10, 2023
Last Verified:	February 2023

Keywords provided by Javad Nazarian, Children's National Research Institute:


diffuse intrinsic pontine glioma DIPG childhood brainstem glioma	pediatric brainstem glioma brainstem glioma BSG

Additional relevant MeSH terms:

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Glioma Diffuse Intrinsic Pontine Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue	Brain Stem Neoplasms Infratentorial Neoplasms Brain Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases

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