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Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial
BACKGROUND: Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570026/ https://www.ncbi.nlm.nih.gov/pubmed/34740331 http://dx.doi.org/10.1186/s12885-021-08878-2 |
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author | Italiano, Antoine Dinart, Derek Soubeyran, Isabelle Bellera, Carine Espérou, Hélène Delmas, Christelle Mercier, Noémie Albert, Sabrina Poignie, Ludivine Boland, Anne Bourdon, Aurélien Geneste, Damien Cavaille, Quentin Laizet, Yec’han Khalifa, Emmanuel Auzanneau, Céline Squiban, Barbara Truffaux, Nathalène Olaso, Robert Gerber, Zuzana Wallet, Cédrick Bénard, Antoine Blay, Jean-Yves Laurent-Puig, Pierre Deleuze, Jean-François Lucchesi, Carlo Mathoulin-Pelissier, Simone |
author_facet | Italiano, Antoine Dinart, Derek Soubeyran, Isabelle Bellera, Carine Espérou, Hélène Delmas, Christelle Mercier, Noémie Albert, Sabrina Poignie, Ludivine Boland, Anne Bourdon, Aurélien Geneste, Damien Cavaille, Quentin Laizet, Yec’han Khalifa, Emmanuel Auzanneau, Céline Squiban, Barbara Truffaux, Nathalène Olaso, Robert Gerber, Zuzana Wallet, Cédrick Bénard, Antoine Blay, Jean-Yves Laurent-Puig, Pierre Deleuze, Jean-François Lucchesi, Carlo Mathoulin-Pelissier, Simone |
author_sort | Italiano, Antoine |
collection | PubMed |
description | BACKGROUND: Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant’s outcome. METHODS: This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm “NGS” and the standard “No NGS”. NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in “No NGS” arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator. DISCUSSION: The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale. TRIAL REGISTRATION: clinicaltrial.gov NCT03784014. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08878-2. |
format | Online Article Text |
id | pubmed-8570026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85700262021-11-08 Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial Italiano, Antoine Dinart, Derek Soubeyran, Isabelle Bellera, Carine Espérou, Hélène Delmas, Christelle Mercier, Noémie Albert, Sabrina Poignie, Ludivine Boland, Anne Bourdon, Aurélien Geneste, Damien Cavaille, Quentin Laizet, Yec’han Khalifa, Emmanuel Auzanneau, Céline Squiban, Barbara Truffaux, Nathalène Olaso, Robert Gerber, Zuzana Wallet, Cédrick Bénard, Antoine Blay, Jean-Yves Laurent-Puig, Pierre Deleuze, Jean-François Lucchesi, Carlo Mathoulin-Pelissier, Simone BMC Cancer Study Protocol BACKGROUND: Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant’s outcome. METHODS: This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm “NGS” and the standard “No NGS”. NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in “No NGS” arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator. DISCUSSION: The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale. TRIAL REGISTRATION: clinicaltrial.gov NCT03784014. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08878-2. BioMed Central 2021-11-05 /pmc/articles/PMC8570026/ /pubmed/34740331 http://dx.doi.org/10.1186/s12885-021-08878-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Study Protocol Italiano, Antoine Dinart, Derek Soubeyran, Isabelle Bellera, Carine Espérou, Hélène Delmas, Christelle Mercier, Noémie Albert, Sabrina Poignie, Ludivine Boland, Anne Bourdon, Aurélien Geneste, Damien Cavaille, Quentin Laizet, Yec’han Khalifa, Emmanuel Auzanneau, Céline Squiban, Barbara Truffaux, Nathalène Olaso, Robert Gerber, Zuzana Wallet, Cédrick Bénard, Antoine Blay, Jean-Yves Laurent-Puig, Pierre Deleuze, Jean-François Lucchesi, Carlo Mathoulin-Pelissier, Simone Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title | Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title_full | Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title_fullStr | Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title_full_unstemmed | Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title_short | Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial |
title_sort | molecular profiling of advanced soft-tissue sarcomas: the multisarc randomized trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570026/ https://www.ncbi.nlm.nih.gov/pubmed/34740331 http://dx.doi.org/10.1186/s12885-021-08878-2 |
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