In Vitro Models From Pediatric Brain Tumors

NCT06499636 | Not Yet Recruiting

• 1 other identifier: 6351
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Tumors of the Central Nervous System (CNS) represent the leading cause of cancer-related deaths in children. Current treatment options are not curative for most malignant histologies, and intense preclinical and clinical research are necessary to develop more effective therapeutic interventions against these tumors, most of which meet the FDA definition for orphan diseases. The majority of malignant CNS tumors in children and adolescents belong to two broad histologic tumor entities: those of glial origin, such as high-grade glioma (HGG)and ependymoma (EPN), and those of neuronal origin, also identified as embryonal tumors, that include medulloblastoma and AT/RT(1). Over the last few years, whole-genome sequencing, gene-expression profiling and genome-wide methylation studies have greatly deepened our understanding of the biology and genetics of these tumors, allowing for robust stratification in clinically relevant molecular subgroups. The advancement of single-cell omics over the last decade have highlighted the enormous heterogeneity of tumors, a complex mixture of co-existing cancer subclones and supportive normal cell populations. However, current treatments have remained largely static, and 5-year survival rate for children with malignant CNS tumors only achieves a modest 57.5%. More effective treatment strategies should include novel chemotherapeutic agents that take into account high intrinsic tumor heterogeneity as well as the complex regulations of transcriptional and translational mechanisms that control protein expression. Identification of novel drugs and treatment strategies is further limited by the paucity of appropriate preclinical models, which mirror the molecular characteristics of distinct tumor subgroups. We propose to establish patient-derived in vitro models to predict chemotherapeutic drug sensitivity/resistance in malignant pediatric CNS tumors. Next, we propose to perform molecular analyses in tissues of pediatric CNS tumors to determine whether in vitro findings have clinical correlates.

Conditions

Glioma, Malignant; Ependymoma; Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• 1) Establishment of in vitro models derived from pediatric tumors of the CNS, which more faithfully mirror the molecular features and heterogeneity of pediatric EPNs.

  Collection and storage of snap-frozen pediatric brain tumor samples (tumor specimens and blood samples). Generation of patient-derived cell lines.

  48 months

Secondary Outcomes (2)

• 2) Preclinical drug testing, to explore the chemotherapeutic potential of selected standard and molecularly-targeted agents.

  24 months

• 3) Molecular studies on pediatric brain tumor tissues, to determine whether the cellular, molecular and biochemical findings in in vitro models have clinical correlates.

  36 months

Interventions

other OTHER

other

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children and young adults

You may qualify if:

• Children and young adults who undergo standard surgical resection for suspected primary brain tumors or recurrent brain tumors
• signed written informed consent

You may not qualify if:

• no informed consent

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Pediatric Oncology Unit- Fondazione Policlinico Gemelli IRCCS

Roma, Rome, 00168, Italy

Location

MeSH Terms

Conditions

Glioma; Ependymoma; Medulloblastoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive

Study Officials

• Antonio Ruggiero, prof

  Fondazione Policlinico Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Ruggiero, prof

CONTACT

00390630155155; antonio.ruggiero@unicatt.it

Tiziana Servidei, PhD

CONTACT

00390630155155; tiziana.servidei@guest.policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 12, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 12, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)