Molecular Profiling of Advanced Soft-tissue Sarcomas

Summary

MULTISARC is a randomized multicenter study assessing whether high throughput molecular analysis (next generation sequencing exome - NGS) is feasible in advanced/metastatic soft-tissue sarcoma patients, that is, whether NGS can be conducted for a large proportion of patients, with results available within reasonnable delays.

In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by high throughput molecular analysis (next generation sequencing exome, RNASeq \[NGS\]) in patients with Advanced/metastatic soft-tissue sarcomas. At the end of first-line treatment, participant's tumor profile of experimental Arm NGS (treatment strategy based on NGS results) will be discussed within a multidisciplinary tumor board which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant. Participants for whom a targetable genomic alteration has been identified will be proposed to enter in one of the subsequent phase II single-arm sub-trial.

Conditions

• Soft Tissue Sarcoma

Interventions

DRUG

Nilotinib

Target: KIT, PDGFRA, CSF1R Nilotinib will be administered orally, 400 mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Ceritinib

Target: ALK, ROS. Ceritinib will be administered orally, 450mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Capmatinib

Target: MET. Capmatinib will be administered orally, 400mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Lapatinib

Target: ERBB2, EGFR. Lapatinib will be administered orally, 1500mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Trametinib

Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K. Trametinib will be administered orally, 2 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

COMBINATION_PRODUCT

Trametinib and Dabrafenib

Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K, BRAF. Trametinib will be administered orally, 2mg once daily on a continuous basis. Dabrafenib will be administered orally, 150mg twice daily, on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

COMBINATION_PRODUCT

Olaparib and Durvalumab

Target: PDL1, PARP. Olaparib will be administered orally, 300mg twice daily on a continuous basis. Dabrafenib will be administered intraveinously, 1500mg on day 1 every 4 weeks. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Palbociclib

Target: CDK4, CDK6. Palbociclib will be administered orally, 125mg once daily, 3 weeks on/1 week off. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

Glasdegib

Target: SMO. Glasdegib will be administered orally, 300 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.

DRUG

TAS-120

Target: FGFR. TAS-120 will be administered orally, 20 mg once daily on a continuous basis. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.

OTHER

Next Generation sequencing exome

Both frozentumor material (archived or newly obtained) and blood sample collection will be used for genetic profiling

Sponsors & Collaborators

• Commissariat A L'energie Atomique

  collaborator OTHER_GOV

• Institut Bergonié

  collaborator OTHER

• Plateforme labellisée Inca - Institut Bergonié, Bordeaux

  collaborator UNKNOWN

• Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris

  collaborator UNKNOWN

• EUCLID Clinical Trial Platform

  collaborator OTHER

• Institut National de la Santé Et de la Recherche Médicale, France

  lead OTHER_GOV

Principal Investigators

• Antoine Italiano · Institut Bergonié

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-19

Primary Completion

2023-12-01

Completion

2026-01-20

Countries

• France

Study Locations