Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2) (InnovRT-2)

Hétérogénéité Des Tumeurs Rhabdoides : Approches en " Cellules Uniques " Pour Identifier Des Cibles thérapeutiques

The aim is to describe at the cellular level the heterogeneity of rhabdoid tumors, and identify how this diversity influences resistance to treatment.

Study Overview

• Status: Recruiting
• Conditions: ATRT
• Intervention / Treatment: Biological: analyzes in singles cells

Detailed Description

Rhabdoid tumors are aggressive cancers of infancy. Although frequently chemosensitive at the very beginning, they very often show resistance, suggesting some intra-tumor diversity or plasticity. Moreover, morphological analysis of rhadoid tumors often reveal some variety in tumor cell shapes and immunohistochemical profiling. Altogether, this suggests some intra-tumor heterogeneity, that has been scarcely studied so far.

This project aims to describe the intra-tumor heterogeneity by single-cell sequencing approaches.

After surgical resection, fresh tumor samples will be dissected and analysed using the 10X Chromium technology. Briefly, cells will be grouped in clusters according to their gene expression signalling, and each cluster will be defined in comparison with all other ones. Differential analyses will allow identifying the main characteristic of each cell sub-population. Potential filiations between clusters will be analysed using classical algorithms. The study will be performed on 10 to 15 tumor samples.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Nelly BRIAND, PhD; Phone Number: 01 44 38 18 62; Email: nelly.briand@aphp.fr
• Study Contact Backup: Name: Franck BOURDEAUT, MD; Phone Number: 01 44 32 44 71; Email: franck.bourdeaut@curie.fr

Study Locations

• France
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
    • Contact: Franck BOURDEAUT, MD; Phone Number: 01 44 32 44 71; Email: franck.bourdeaut@curie.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children having or likely having a rhabdoid tumor according to clinical and radiological features

Description

Inclusion Criteria:

• Aged 0-17 years old
• having a rhabdoid tumor according to clinical and radiological features Or likely having a rhabdoid tumor according to clinical and radiological features
• surgical resection in standard care
• sufficient material for both diagnosis and experimental procedures
• parents' agreement

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ATRT; Children affected by an ATRT at time of surgical resection	Biological: analyzes in singles cells; genome expression analyzes in single cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-tumor heterogeneity	Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster	Inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell clusters recurrent from one sample to the other	Fraction/percentage of cell clusters defined by primary outcome that are specific to each tumor and those that are shared by several or all samples	Inclusion
Naming of potential targetable gene	Mean expression (RPKM unit) of targetable genes (defined by the existence of adequate pharmacological inhibitor) in each tumor sample and clusters	Inclusion
Identification of cytotoxic cells	Conducting therapeutic biological functional tests	Inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut Curie
• Investigators: Study Director: Kevin Beccaria, MD, PhD, Pr, APHP Assistance Publique des Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: July 31, 2021
• First Submitted That Met QC Criteria: July 31, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: ATRT; SMARCB1; single-cell RNAseq
• Other Study ID Numbers: APHP200122; 2021-A00795-36 (Other Identifier: ID-RCB Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No