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Proteomic Characterization of Aggressive Oligodendrogliomas

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages N/A and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

- - 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)

Exclusion Criteria:

- opposed patients

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04843085
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hospices Civils de Lyon
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Unknown status
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Oligodendroglioma
Arms & Interventions

Arms

: O1

the more aggressive subgroup of oligodendroglioma samples of 30 patients

: O2

subgroup 2 of oligodendroglioma samples of 30 patients

: O3

subgroup 3 of oligodendroglioma samples of 30 patients

: IDH-mutant astrocytomas

patients with IDH-mutant astrocytomas, samples of 15 patients

: IDH-wildtype glioblastomas

patients with IDH-wildtype glioblastomas, samples of 15 patients

Interventions

Other: - Proteomic analysis

: 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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Groupement Hospitalier Est HCL, Bron, France

Status

Recruiting

Address

Groupement Hospitalier Est HCL

Bron, ,

Site Contact

François Ducray, MD

[email protected]

04 72 35 78 06

Institut du Cerveau et de la Moelle, Paris, France

Status

Not yet recruiting

Address

Institut du Cerveau et de la Moelle

Paris, ,