Proteomic Characterization of Aggressive Oligodendrogliomas

Oligodendroglioma Clinical Trial

— PROGLIO  

Official title:

Proteomic Characterization of Aggressive Oligodendrogliomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04843085
• Other study ID #: 69HCL20_0074
• Status: Recruiting
• Start date: September 30, 2020
• Est. completion date: September 2023

Study information

• Verified date: December 2020
• Source: Hospices Civils de Lyon
• Contact: François DUCRAY, MD
• Phone: 04 72 35 78 06
• Email: francois.ducray[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 2023
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Oligodendroglioma

Intervention

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

Locations

Country	Name	City	State
France	Groupement Hospitalier Est HCL	Bron
France	Institut du Cerveau et de la Moelle	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)