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

BMC Cancer. 2021 Nov 5;21(1):1180. doi: 10.1186/s12885-021-08878-2.

Abstract

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 .

Keywords: Biomarker-driven; Next generation sequencing; Soft-tissue sarcomas; Umbrella.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Cost-Benefit Analysis
  • Exome Sequencing
  • Feasibility Studies
  • France
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Multicenter Studies as Topic
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Sample Size
  • Sarcoma* / genetics
  • Sarcoma* / pathology
  • Sarcoma* / therapy
  • Soft Tissue Neoplasms* / genetics
  • Soft Tissue Neoplasms* / pathology
  • Soft Tissue Neoplasms* / therapy
  • Time Factors

Associated data

  • ClinicalTrials.gov/NCT03784014