Molecular Profiling of Advanced Soft-tissue Sarcomas

NCT03784014 | Completed Phase 3 DMC

• 3 other identifiers: C16-402024-514873-22-002017-002851-27
• Study Type: interventional
• Target: 603
• Locations: 1 country
• Sites: 17

Brief 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

Keywords

advanced disease; metastatic disease; Next generation sequencing exome

Outcome Measures

Primary Outcomes (1)

• To assess the feasibility of high throughput molecular analysis (next generation sequencing exome [NGS]

  Feasibility will be defined as the proportion of participants for whom results from NGS are (i) interpretable and (ii) for whom a validated report of exome sequencing including a clinical recommendation from the molecular tumor board is available within 7 weeks (i.e. within at most 49 calendar days) after reception of blood and tumor samples by one of the molecular platform.

  7 weeks

Secondary Outcomes (25)

• Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year progression-free survival (PFS)

  1 year

• Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year progression-free survival (PFS)

  2 years

• Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year overall survival (OS)

  1 year

• Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year overall survival (OS)

  2 years

• Assessment of the feasibility of high throughput molecular analysis in terms of delay to obtain a clinical recommendation from the molecular tumor board for patients randomized in arm NGS with interpretable NGS

  an average of 7 weeks

Study Arms (3)

Arm No NGS

NO INTERVENTION

Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. Thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment. Note that for these participants and under specific conditions, subsequent NGS analyses may be allowed within the scope of the trial

Arm NGS

EXPERIMENTAL

Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. After tumor assessment at the end of first-line systemic treatment and regardless of tumor response as per RECIST v1.1, participants will be discussed within a multidisciplinary tumor board (molecular tumor board-MTB) which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant. Patients for whom a targetable genomic alteration has been highlighted will be proposed to enter in a subsequent single-arm phase II sub-trials. Otherwise, thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment

Other: Next Generation sequencing exome

Arm NGS - Targeted therapy

EXPERIMENTAL

Targeted therapy from a list of 10 targeted treatment strategies, guided by the genomic analyses: Nilotinib capsule per os 400 mg bd, continuous dosing ; Ceritinib capsule per os 450 mg od, continuous dosing; Capmatinib tablet per os 400 mg bd, continuous dosing; Lapatinib tablet per os 1500 mg od, continuous dosing; Trametinib tablet per os 2 mg od, continuous dosing; association of Trametinib tablet per os 2 mg od and Dabrafenib capsule per os 150 mg bd, continuous dosing; association of Olaparib tablet per os 300 mg bd, continuous dosing and Durvalumab intra-veinous 1500 mg on day 1, Q4W; Palbociclib capsule 125 mg od, 3 weeks on/1 week off; Glasdegib tablet per os 300 mg od, continuous dosing; TAS-120 tablet per os 20 mg od, continuous dosing.

Drug: Nilotinib; Drug: Ceritinib; Drug: Capmatinib; Drug: Lapatinib; Drug: Trametinib; Combination Product: Trametinib and Dabrafenib; Combination Product: Olaparib and Durvalumab; Drug: Palbociclib; Drug: Glasdegib; Drug: TAS-120

Interventions

Trametinib DRUG

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.

Also known as: MEKINIST

Arm NGS - Targeted therapy

Trametinib and Dabrafenib COMBINATION_PRODUCT

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.

Also known as: MEKINIST and TAFINLAR

Arm NGS - Targeted therapy

Olaparib and Durvalumab COMBINATION_PRODUCT

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.

Also known as: LYNPARZA, MEDI4736

Arm NGS - Targeted therapy

Palbociclib DRUG

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.

Also known as: IBRANCE, PD-0332991

Arm NGS - Targeted therapy

Glasdegib DRUG

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.

Also known as: PF-04449913

Arm NGS - Targeted therapy

TAS-120 DRUG

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.

Arm NGS - Targeted therapy

Next Generation sequencing exome OTHER

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

Also known as: RNA Seq, NGS, High throughput sequencing

Arm NGS

Nilotinib DRUG

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.

Also known as: TASIGNA

Arm NGS - Targeted therapy

Ceritinib DRUG

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.

Also known as: ZYKADIA

Arm NGS - Targeted therapy

Capmatinib DRUG

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.

Arm NGS - Targeted therapy

Lapatinib DRUG

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.

Also known as: TYVERB

Arm NGS - Targeted therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years,
• Histology: soft-tissue sarcoma confirmed by the RRePS Network, as recommended by the French NCI
• Unresectable locally advanced and/or metastatic STS
• No previous systemic treatment for advanced disease,
• ECOG ≤ 1
• Adequate hematological and metabolic functions: Hemoglobin \> 9 g/dL and albumin \> 30 g/L
• Measurable disease according to RECIST 1.1. At least one site of disease must be uni-dimensionally \> 10 mm,
• Availability of suitable frozen archive tumor material obtained from a metastatic lesion or advanced disease (not previously treated), or at least one lesion that can be biopsied for research purpose,
• Archived FFPE block of specimen tumor sampling obtained anytime during disease development for research purpose,
• Eligible to first-line systemic treatment,
• Participant with a social security in compliance with the French law,
• Voluntary signed and dated written informed consent prior to any study specific procedure (ICF1)

You may not qualify if:

• Radiological evidence of symptomatic or progressive brain metastases,
• Inability to swallow,
• Major problem with intestinal absorption,
• Previous allogeneic bone marrow transplant,
• Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV or active autoimmune disease),
• Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol,
• Individuals deprived of liberty or placed under guardianship
• Pregnant or breast feeding women,
• Men or women refusing contraception,
• Previous enrolment in the present study,
• Any contraindication to first-line chemotherapy treatment.
• Phase II Sub-trials
• Participants already enrolled in MULTISARC and randomized/switched in Arm "NGS",
• ECOG performance status \< 1,
• Measurable disease according to RECIST v1.1,

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• Commissariat A L'energie Atomique: collaborator
• Plateforme labellisée Inca - Institut Bergonié, Bordeaux: collaborator
• Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris: collaborator
• EUCLID Clinical Trial Platform: collaborator
• Institut Bergonié: collaborator

Study Sites (17)

Institut Bergonie

Bordeaux, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut de Cancérologie de Montpellier

Montpellier, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Pitié Salpétrière

Paris, France

Location

Institut Curie

Paris, France

Location

CHU Poitiers

Poitiers, 86000, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, France

Location

ICANS - Institut de Cancérologie Strasbourg

Strasbourg, 67033, France

Location

IUCT Oncopôle

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (3)

• Italiano A. Is There Value in Molecular Profiling of Soft-Tissue Sarcoma? Curr Treat Options Oncol. 2018 Dec 7;19(12):78. doi: 10.1007/s11864-018-0589-y.

  PMID: 30523434 BACKGROUND

• FGM 2025 Workflow Study Group (Alliance nationale des Sciences de la Vie et de la Sante); Auzanneau C, Bacq D, Bellera C, Blons H, Boland A, Boucheix M, Bourdon A, Chollet E, Chomienne C, Deleuze JF, Delmas C, Dinart D, Esperou H, Geillon F, Geneste D, Italiano A, Jean D, Khalifa E, Laizet Y, Laurent-Puig P, Lethimonnier F, Levy-Marchal C, Lucchesi C, Malle C, Mancini P, Mathoulin-Pelissier S, Meyer V, Marie-Ange P, Perkins G, Sellan-Albert S, Soubeyran I, Wallet C. Feasibility of high-throughput sequencing in clinical routine cancer care: lessons from the cancer pilot project of the France Genomic Medicine 2025 plan. ESMO Open. 2020 Jul;5(4):e000744. doi: 10.1136/esmoopen-2020-000744.

  PMID: 32713836 RESULT

• Italiano A, Dinart D, Soubeyran I, Bellera C, Esperou H, Delmas C, Mercier N, Albert S, Poignie L, Boland A, Bourdon A, Geneste D, Cavaille Q, Laizet Y, Khalifa E, Auzanneau C, Squiban B, Truffaux N, Olaso R, Gerber Z, Wallet C, Benard A, Blay JY, Laurent-Puig P, Deleuze JF, Lucchesi C, Mathoulin-Pelissier S; MULTISARC study group. 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.

  PMID: 34740331 RESULT

MeSH Terms

Conditions

Sarcoma; Neoplasm Metastasis

Interventions

nilotinib; ceritinib; capmatinib; Lapatinib; trametinib; dabrafenib; olaparib; durvalumab; palbociclib; glasdegib; futibatinib; Base Sequence; High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Antoine Italiano

  Institut Bergonié

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: MULTISARC is a randomized multicenter study assessing whether high throughput molecular analysis (next generation sequencing exome - NGS) is feasible in advanced soft tissue sarcoma participants. In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by high throughput molecular analysis, in participants with advanced soft-tissue sarcomas. Randomization 1:1 with 1 participant randomized in experimental Arm NGS (treatment strategy based on NGS) and 1 participant randomized in standard Arm No NGS (treatment strategy not based on NGS). At the end of first-line treatment, participant's tumor profile of experimental Arm NGS 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.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: October 19, 2019
• Primary Completion: December 1, 2023
• Study Completion: January 20, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (17)