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

NCT ID: NCT01106794

Last Updated: 2024-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-04-30

Study Completion Date

2030-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diffuse Intrinsic Pontine Glioma Brainstem Glioma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

Eligibility Criteria

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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)
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's National Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Javad Nazarian

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Javad Nazarian, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Locations

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Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Javad Nazarian, PhD

Role: CONTACT

202-476-6022

Caroline Kopsidas, BS

Role: CONTACT

240-393-3359

References

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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.

Reference Type BACKGROUND
PMID: 20197468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26206682 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25987129 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25749048 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32616776 (View on PubMed)

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.

Reference Type RESULT
PMID: 24076776 (View on PubMed)

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.

Reference Type RESULT
PMID: 22492959 (View on PubMed)

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.

Reference Type RESULT
PMID: 24894482 (View on PubMed)

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.

Reference Type RESULT
PMID: 24705254 (View on PubMed)

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.

Reference Type RESULT
PMID: 24297113 (View on PubMed)

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.

Reference Type RESULT
PMID: 27048880 (View on PubMed)

Related Links

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https://childrensnational.org/research

Children's National Medical Center

Other Identifiers

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DIPG-1

Identifier Type: -

Identifier Source: org_study_id

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