Neoplasms

All Conditions

Rare Diseases

Rhabdoid Tumor

Children affected by an ATRT at time of surgical resection

genome expression analyzes in single cells

analyzes in singles cells

Franck BOURDEAUT, MD

Nelly BRIAND, PhD

Kevin Beccaria, MD, PhD, Pr

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

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.

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

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

Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster

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

Mean expression (RPKM unit) of targetable genes (defined by the existence of adequate pharmacological inhibitor) in each tumor sample and clusters

Conducting therapeutic biological functional tests

Institut Curie

Assistance Publique - Hôpitaux de Paris

Nervous System Diseases

Brain Neoplasms

Patients \<18 years with an ATRT having frozen samples

Characterization of the proteomic and phosphoproteomic landscape using mass spectrometry

Mass spectrometry

Kevin Beccaria, MD, PhD

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.

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.

Finding New Targets by Proteomic Approaches (InnovRT1)

Heterogeneity in Rhabdoid Tumors : Proteomic and Single-Cell Analyses to Identify New Therapeutic Targets

Sainte Anne hospital

Skin and Connective Tissue Diseases

Sarcoma

Sarcoma, Synovial

Chordoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Synovial Sarcoma

Epithelioid Sarcoma

Dermatologic Agents

All Drugs and Chemicals

Coal Tar

Up to approximately 104 patients will be enrolled in dose escalation and expansion.

FHD-609 as a single, intravenously administered agent given twice-weekly (BIW). Alternative dosing regimens may be evaluated.

FHD-609

Sarah Reilly, MD

This Phase 1, multicenter, open-label, dose escalation and expansion study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-609 given intravenously in subjects with advanced synovial sarcoma or advanced SMARCB1-loss tumors.

This study is an ascending multiple dose clinical trial with expansion arms. It is primarily intended to evaluate the safety and tolerability of FHD-609 when administered intravenously to subjects with advanced synovial sarcoma or advanced SMARCB1-loss tumors. The Dose Escalation Phase will allow for the determination of the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of FHD-609. This study will also evaluate the PK/PD profiles of multiple dose administration of FHD-609.

The Dose Expansion Phase will allow a more robust evaluation of the safety profile of FHD-609, including toxicities that may occur less frequently, and an assessment of anti-tumor activity. The data from this study in subjects with advanced synovial sarcoma, including safety, tolerability, PK/PD findings, and anti-tumor activity, will form the basis for subsequent clinical development of FHD-609.

Open label single arm dose escalation and three-arm expansion study in patients with advanced synovial sarcoma or advanced SMARCB1-loss tumors

FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors

A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors

During first 6 weeks of treatment for each patient in dose escalation

ORR is defined as the percentage of subjects achieving a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

DOR is defined as the time from first documented evidence of CR or PR until the earliest date of documented radiological progression per RECIST 1.1. or death due to any cause among subjects who achieved a CR or PR

PFS defined as the time from first dose of study treatment until the first date of either objective disease progression per RECIST 1.1. or death due to any cause, whichever happens first

TTR is defined as the period of time from the date of first study drug administration until the first objective documentation of response per RECIST 1.1.

OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death.

Plasma concentration of FHD-609 at the scheduled timepoints

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2)	NCT04987476	ATRT	analyzes in sin...	- 17 Years	Assistance Publique - Hôpitaux de Paris
Finding New Targets by Proteomic Approaches (InnovRT1)	NCT04868799	ATRT	Mass spectromet...	- 17 Years	Assistance Publique - Hôpitaux de Paris
FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors	NCT04965753	Advanced Synovi...	FHD-609	16 Years -	Foghorn Therapeutics Inc.

Spots Global Cancer Trial Database for smarcb1

Every month we try and update this database with for smarcb1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for smarcb1

Every month we try and update this database with for smarcb1 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for smarcb1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.