Proteomic Characterization of Aggressive Oligodendrogliomas

NCT04843085 | Unknown

• 1 other identifier: 69HCL20_0074
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

Oligodendrogliomas represent a distinct subgroup of adult gliomas characterized by specific molecular alterations (1p/19q codeletion, mutations of IDH, TERT promoter, CIC, FUBP1). These tumors account for 5 to 10% of adult gliomas and are of special relevance in the neuro-oncology field because of their frequent chemosensitivity (Louis et al. 2016). The genetics of oligodendrogliomas is relatively well characterized but the mechanisms of oncogenesis for these tumors are poorly understood. Although oligodendrogliomas prognosis is usually better than that of other adult glioma subtypes, it remains heterogeneous and there is no effective treatment at recurrence after radiotherapy and chemotherapy. Our recent work conducted within the INCa-funded national POLA network has related this clinical heterogeneity to inter-tumoral heterogeneity. Based on a transcriptomic analysis of a large series of oligodendroglial gliomas we identified 3 subgroups, the most aggressive group being characterized by aggressive clinical and molecular pattern. Recent studies, however, have shown a relatively low level of concordance between mRNA and protein expression, emphasizing the need to use proteomic-based approaches to better understand tumor biology. Taking advantage of the POLA cohort, we propose to expand our previous analysis by integrating a proteomic analysis of oligodendrogliomas. The aim of this project is to identify drivers of oligodendroglioma subgroups, among which potential druggable targets (i.e receptors, metabolism effectors). For this purpose, the proteomic profiles of 90 oligodendrogliomas will be generated and integrated with transcriptomic, genomic and methylation profiles in order to identify signaling pathways specifically associated with each subtype, especially with the most aggressive one. Associations will be explored between candidate signaling pathways expression and clinical outcomes (survival, progression-free survival, objective response). The relevance of the 2 most promising candidate signaling pathways will be assessed in vitro and in vivo using genetically relevant mouse and xenograft models. Our project will identify targetable oncogenic pathways associated with poor prognosis that could lead to new therapeutic strategies.

Conditions

Oligodendroglioma

Keywords

Oligodendroglioma; proteomic analysis; POLA network

Outcome Measures

Primary Outcomes (1)

• proteomic profiles

  Concordance of the classification of oligodendrogliomas based on their proteomic profiles with our previously identified oligodendrogliomas subgroups.

  Baseline (at time of diagnosis surgery)

Study Arms (5)

O1

the more aggressive subgroup of oligodendroglioma samples of 30 patients

Other: Proteomic analysis

O2

subgroup 2 of oligodendroglioma samples of 30 patients

Other: Proteomic analysis

O3

subgroup 3 of oligodendroglioma samples of 30 patients

Other: Proteomic analysis

IDH-mutant astrocytomas

patients with IDH-mutant astrocytomas, samples of 15 patients

Other: Proteomic analysis

IDH-wildtype glioblastomas

patients with IDH-wildtype glioblastomas, samples of 15 patients

Other: Proteomic analysis

Interventions

Proteomic analysis OTHER

: Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples

IDH-mutant astrocytomas; IDH-wildtype glioblastomas; O1; O2; O3

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

samples of patients with oligodendrolioma, astrocytoma, glioblastoma and normal brain available in the POLA network biobank or the OncoNeuroTek tumor bank (Institut du Cerveau et de la Moelle Épinière)

You may qualify if:

• \- transcriptomic (microarray) data available or possible to obtain them,
• methylation (450K) data available or possible to obtain them,
• genomic (SNP array) data available or possible to obtain them,
• sufficient material for proteomic analysis (frozen tumor samples)

You may not qualify if:

• opposed patients

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Groupement Hospitalier Est HCL

Bron, France

RECRUITING

Institut du Cerveau et de la Moelle

Paris, France

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

tumoral sample and blood

MeSH Terms

Conditions

Oligodendroglioma

Condition Hierarchy (Ancestors)

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

Central Study Contacts

François DUCRAY, MD

CONTACT

04 72 35 78 06; francois.ducray@chu-lyon.fr

Study Design

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

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: April 13, 2021
• Study Start: September 30, 2020
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2023
• Last Updated: April 13, 2021

Record last verified: 2020-12

Locations

FR (2)