Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial

BMC Cancer

Noémie Mercier¹  Ludivine Poignie²  Céline Auzanneau³  Isabelle Soubeyran³  Barbara Squiban³  Emmanuel Khalifa³  Nathalène Truffaux³  Jean-Yves Blay⁴  Antoine Italiano⁵  Hélène Espérou⁶  Christelle Delmas⁶  Pierre Laurent-Puig⁷  Carlo Lucchesi⁸  Quentin Cavaille⁸  Damien Geneste⁸  Aurélien Bourdon⁸  Yec’han Laizet⁸  Cédrick Wallet⁹  Antoine Bénard⁹  Sabrina Albert^1,10  Simone Mathoulin-Pelissier^1,10  Carine Bellera^1,10  Derek Dinart^1,11  Jean-François Deleuze^1,12  Zuzana Gerber^1,12  Robert Olaso^1,12  Anne Boland^1,12 

[1] ANRS (France Recherche Nord&sud Sida-hiv Hépatites), Clinical Trial Safety and Public Health, Paris, France;Clinical Research and Clinical Epidemiology Unit, Institut Bergonié, Bordeaux, France;Department of Biopathology, Institut Bergonié, U1218, Bordeaux, France;Department of Medical Oncology, Centre Léon Bérard, Lyon, France;Department of Medical Oncology, Institut Bergonié, University of Bordeaux, INSERM, Unité ACTION U1218, Bordeaux, France;Inserm, Pôle de Recherche Clinique, 75013, Paris, France;Sorbonne Paris Cité, Paris Descartes University, Georges Pompidou European Hospital, Paris, France;U1218, Institut Bergonié, Institut national de la santé et de la recherche médicale, Bordeaux, France;Bioinformatics unit, Institut Bergonié, Bordeaux, France;University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CIC-EC 1401/EUCLID Clinical Trials Platform, Bordeaux, France;CHU, Bordeaux, France;University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CIC-EC 1401/EUCLID Clinical Trials Platform, Bordeaux, France;Clinical Research and Clinical Epidemiology Unit, Institut Bergonié, Bordeaux, France;University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CIC-EC 1401/EUCLID Clinical Trials Platform, Bordeaux, France;Unité de pathologie moléculaire, Institut Bergonié, Bordeaux, France;Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France;

关键词: Next generation sequencing;    Soft-tissue sarcomas;    Umbrella;    Biomarker-driven;   

DOI  :  10.1186/s12885-021-08878-2

来源: Springer

【 摘 要 】

BackgroundSoft-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.MethodsThis 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.DiscussionThe 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 registrationclinicaltrial.gov NCT03784014.

【 授权许可】

CC BY