Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Molecular Characterization of Genetic Alterations in Pediatric Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04773808
Recruitment Status : Recruiting
First Posted : February 26, 2021
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
Maria Victoria Preciado, National Council of Scientific and Technical Research, Argentina

Brief Summary:

Background: In Argentina, central nervous system (CNS) solid tumors (19%) and non-CNS solid tumors (25%) account for 44% of pediatric tumors. The new World Health organization (WHO) 2016 classification, which includes genomic characterization, comprises more than 100 CNS tumor entities and subclasses. In children, glial lineage tumors (gliomas) are the most frequent and comprise astrocytomas, ependymomas and oligodendroglioma, while embryonal CNS tumors are a heterogeneous group of WHO grade IV tumors. Pediatric soft tissue tumors (STT) present difficulties for accurate diagnosis since their morphological and immunophenotypic features overlap among the different histological patterns.

The emergence of new molecular techniques has generated a great advance in the field of solid tumors, particularly in the molecular definition of groups of patients. This fact makes tailor-made treatment feasible, according to the biology of the tumor.

In particular, in children, the identification of treatment targets is especially important since it may avoid unnecessary sequel in a growing child. This project allows the articulation between basic and clinical research groups, thus consolidating the objective of basic translational research and generating both clinical and basic knowledge about the pathogenesis of pediatric solid tumors in our country.

Aim: To standardize and implement a comprehensive multi-level molecular strategy, using medium and high complexity techniques, for the detection of molecular alterations in primary pediatric solid tumors (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal)), that can be applied to the diagnosis, prognosis and/or use of targeted therapies against molecular targets in order to provide a tailored therapeutic opportunity.

Material and methods: Pediatric cases of solid tumors will be enrolled prospectively. Based on the statistics of the participating centers, 100 samples will be included. From each case, a formalin fixed biopsy will be available and when possible, a fragment will also be preserved at -70ºC. Clinical and follow-up data will be obtained from the clinical records.

The methodological approaches include: 1) Immunohistochemical detection of tumor lineage determinant markers, some of them with predictive value. 2) FISH (fluorescence in situ hybridization) with break-apart strategy for genes involved in recurrent chromosomal translocations and locus-specific design probes for other unbalanced structural chromosomal structural alterations (amplifications and deletions of genes or chromosomal segments). 3) Real time (RT)-polymerase chain reaction (PCR) detection of fusion transcripts resulting from chromosomal translocations. 4) Quantitative polymerase chain reaction (qPCR) and Sanger sequencing analysis of single nucleotide polymorphisms (SNPs) as targets for therapy. 5) Sanger sequencing analysis of fusions, ins/del as a complement to RT-PCR or FISH (fluorescence in situ hybridization), 6) Next Generation Sequencing (NGS) with a specific and customized panel containing all necessary genes to define a tumor´s genomic mutation profile for diagnosis, risk stratification and prognosis of pediatric tumors. However, NGS sequencing will only be applied in those cases which could not be resolved with the previous strategies or cases with poor evolution

Based on the above analyses, an integrated analysis algorithm will be developed according to WHO recommendations, but adapted to the facilities of the institution. Molecular findings will be correlated with clinical and histological data


Condition or disease
Pediatric Solid Tumors

Layout table for study information
Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Implementation of a Comprehensive Multi-level Molecular Strategy for the Identification of Genetic Alterations in Pediatric Solid Tumors Aimed at Achieving a Personalized Approach to the Patient
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : February 1, 2026
Estimated Study Completion Date : February 1, 2026



Primary Outcome Measures :
  1. molecular profiling of solid tumors [ Time Frame: 5 years ]
    Perform molecular identification of genetic alterations in neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal)


Secondary Outcome Measures :
  1. molecular markers analysis vby immunohistochemistry [ Time Frame: 5 years ]
    1) Perform immunohistochemical analysis of tumor lineage determinant markers some of them with predictive value

  2. molecular markers analysis by fluorescence in situ hybridization [ Time Frame: 5 years ]
    2) Perform FISH (fluorescence in situ hybridization) analysis of recurrent chromosomal translocations and structural chromosomal alterations

  3. molecular markers analysis by gene amplification [ Time Frame: 5 years ]
    3) Perform RT-qPCR analysis for gene translocations and qPCR analysis for reported SNPs

  4. molecular markers analysis by sequencing [ Time Frame: 5 years ]
    4) Perform complementary Sanger sequencing analysis for SNPs and translocations of unresolved cases

  5. molecular markers analysis by Next Generation Sequencing [ Time Frame: 5 years ]
    5) Perform Next Generation Sequencing (NGS) with a specific and customized panel to define a tumor genomic mutation profile important in the diagnosis, risk stratification and prognosis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients identified at Hospital de Niños R Gutierrez and collaborating institutions with a suspected or known diagnosis of neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal), based on initial diagnosis through clinical examination, laboratory testing and images of a mass ameneable to excision
Criteria

Inclusion Criteria:

  1. Must have a suspected or known diagnosis of neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal) based on the initial diagnostic workup and evidence of gross disease amenable to excision. Specimens may be collected at some or all of the following time points: initial biopsy, tumor resection and at time of possible relapse.
  2. The patient or his/her legal guardian, as appropriate, must provide written informed consent within 30 days of the removal of the first collection of tissue sample for this protocol.
  3. The patient is being seen at Hospital de Niños R Gutierrez or at a collaborating institution.
  4. Patients must be less than or equal to 18 years old at the time of enrollment.

Exclusion Criteria:

  1. No access to the tumor tissue sample.
  2. written informed consent is not obtained.

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): NCT04773808


Contacts
Layout table for location contacts
Contact: Maria Victoria Preciado, PhD +5491144916970 mvpreciado67@gmail.com

Locations
Layout table for location information
Argentina
Maria Victoria Preciado Recruiting
Ciudad Autónoma de Buenos Aires, Argentina, 1425
Contact: Maria Victoria Preciado, Ph.D    1144916970    mvpreciado67@gmail.com   
Sponsors and Collaborators
National Council of Scientific and Technical Research, Argentina
Layout table for additonal information
Responsible Party: Maria Victoria Preciado, Director of Multidisciplinary Institute for Research of Pediatric Pathologies, National Council of Scientific and Technical Research, Argentina
ClinicalTrials.gov Identifier: NCT04773808    
Other Study ID Numbers: Solid Tumors 2020
First Posted: February 26, 2021    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maria Victoria Preciado, National Council of Scientific and Technical Research, Argentina:
pediatric solid tumor
molecular marker
molecular tumor profile
tailored therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms