Clinical trial NCT04868799: Finding New Targets by Proteomic Approaches (InnovRT1)
Official title: Heterogeneity in Rhabdoid Tumors : Proteomic and Single-Cell Analyses to Identify New Therapeutic Targets
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ATRT
Keywords: SMARCB1
ATRT
Brain Tumors
Proteomic
Multi-omics
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Curie
name: Sainte Anne hospital
First posted: 2021-05-03
Enrollment: 44
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: cohort of clinically, radiologically and histopathologically annoted ATRT

Brief summary: The investigators aim to explore the inter tumor heterogeneity by a proteomic approach of a wide series of rhabdoid tumors, from both intra and extra cranial origins.

Detailed description: Context: Rhaboid tumors (RT) are aggressive cancers of young infants, exposed to the toxicity of heavy treatments often ineffective, which justifies the need to identify new treatment strategies. These tumors are characterized by the biallelic alteration of SMARCB1 gene, encoding one of the subunits of the SWI/SNF complex, a chromatin remodeler. These mutations are the only ones found in these very stable cancers, which offers few therapeutic targets that can be identified by genomic techniques. They are morphologically undifferentiated and pluriphenotypic, suggesting the existence of a cellular diversity still poorly described. To advance on these questions, the investigators' laboratory has developed a model of genetically engineered mouse model spontaneously developing RT, biologically very similar to their human counterparts.

Objectives and methods: The investigators' project aims to describe the proteomic and phosphoproteomic signatures of these tumors, so far described at the genome and transcriptome level; an integration of these pangenomic / pan-proteomic studies will reveal the most relevant features to target. The investigators will fully characterize the proteomic and phosphoproteomic landscape using mass spectrometry on a cohort of clinically, radiologically and histopathologically annoted ATRT, for which methylome and RNAseq profiling will also be done. The investigators will describe the proteomic features of each molecularly defined subgroups, and aim to correlate RNAseq changes with proteomic features.

Patients will be included if they or their legal representative have given a consent to such a study, and if frozen material is stored at Necker Hospital.

Expected results: This analysis helps to identify how to articulate several innovative therapeutic approaches, taking into account both the diversity of the cells to be treated, and the real targets, proteins, to inhibit or restore.

Eligibility criteria: Inclusion Criteria:

* Aged 0-17 years old
* Rhabdoid tumor, treated in oncology departments in Ile de France
* frozen samples collected in usual care
* parents' agreement for samples collection in usual care

Exclusion Criteria

* Unconfirmed diagnosis of Rhabdoid tumor with molecular analyses Samples
* paraffin embedded tissues

Primary outcomes:
measure: Identification of proteomic signature for each molecular subgroup of ATRT
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de neurochirurgie - Hôpital Necker Enfants malades
Study officials:
affiliation: APHP Assistance Publique des Hôpitaux de Paris
name: Kevin Beccaria, MD, PhD
role: STUDY_DIRECTOR
References: