Molecular Profiling of Advanced Soft-tissue Sarcomas

NCT ID: NCT03784014

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

603 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-19

Study Completion Date

2026-01-13

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Screening phase: frozen tumor sample (archived or newly obtained) and blood sample will be used for genetic profiling. Patients can be considered as pre-eligible for the randomized phase when all genetic material have been received by the Platform.

Randomization phase: the randomization will allocate the following arms with a ratio 1:1:

* experimental Arm NGS : treatment strategy based on NGS results \[exome, RNASeq\]
* standard Arm No NGS: treatment strategy not based on NGS (Note that for these participants and under specific conditions, subsequent NGS analyses may be allowed within the scope of the trial)

Single-arm phase II sub-trial: at the end of the first-line treatment and regardless of tumor response as per RECIST v1.1, patients randomized in Arm NGS and for whom a targetable alteration has been identified by the Molecular Tumor Board will be considered as pre-eligible for the targeted sub-study. The mandatory post-chemotherapy wash-out period of 21 days will provide time to achieve all the required tests and examinations.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Soft Tissue Sarcoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm No NGS

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Arm NGS

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

Group Type EXPERIMENTAL

Next Generation sequencing exome

Intervention Type OTHER

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

Arm NGS - Targeted therapy

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.

Group Type EXPERIMENTAL

Nilotinib

Intervention Type 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.

Ceritinib

Intervention Type 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.

Capmatinib

Intervention Type 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.

Lapatinib

Intervention Type 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.

Trametinib

Intervention Type 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.

Trametinib and Dabrafenib

Intervention Type 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.

Olaparib and Durvalumab

Intervention Type 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.

Palbociclib

Intervention Type 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.

Glasdegib

Intervention Type 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.

TAS-120

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type 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.

Intervention Type COMBINATION_PRODUCT

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Next Generation sequencing exome

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

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

TASIGNA ZYKADIA TYVERB MEKINIST MEKINIST and TAFINLAR LYNPARZA MEDI4736 IBRANCE PD-0332991 PF-04449913 RNA Seq NGS High throughput sequencing

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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,
* No prior or concurrent malignant disease diagnosed or treated in the last two years before inclusion. Note that patients with in situ carcinoma of the cervix, or adequately treated basal cell or squamous cell carcinoma of the skin, or adequately treated localized prostate cancer, or other localized cancer under maintenance therapy can be included as long as they don't limit assessment of efficacy of first-line systemic therapy,
* 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)


* Participants already enrolled in MULTISARC and randomized/switched in Arm "NGS",
* ECOG performance status \< 1,
* Measurable disease according to RECIST v1.1,
* Molecular alteration identified by molecular profiling,
* Participants who have received a first-line systemic treatment at the inclusion,
* Participants must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
* Participants will have had a minimum of 21 days gap from last chemotherapy or immunotherapy or any other pharmacological therapy and/or radiotherapy prior to the first dose of study treatment,
* Women of childbearing potential must have a negative serum pregnancy test within 3 days of enrolment and serum/urine pregnancy test within 24 hours prior to the administration of the study drug,
* Female with child bearing potential and male participants with partners of child bearing potential must be willing to use two effectives forms of contraception (1 highly effective method and 1 barrier method), from beginning 3 weeks before the first dose of investigational product and until 3 months after discontinuing the study.
* Participant with a social security in compliance with the French law,
* Voluntary signed and dated written informed consent (ICF2) prior to any study specific procedure.

* Previous allogeneic bone marrow transplant,
* Altered hematopoietic or organ function,
* Mean resting corrected QT interval (QTcF)\>470msec obtained from 3 consecutive ECGs
* Previous or current maligancies of other histologies within the last 2 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin and prostate cancer,
* Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses), active uncontrolled systemic bacterial, viral, or fungal infection \> Grade 2 as per NCI CTCAE v5.0
* Chronic or active hepatitis B or hepatitis C. Testing for hepatitis B surface antigen (HBs Ag) and hepatitis B core antibody (anti HBc) will be performed at screening,
* Human immunodeficiency virus (HIV) positive,
* 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.

Exclusion Criteria

* 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


* Previous treatment with the targeted therapy,
* No "targetable" genomic alteration generated during the screening phase either due to the lack of alteration or due to ineligible samples for genomic analysis (MULTISARC),
* Participants with total gastrectomy,
* Major surgery within 30 days prior to entry into the study (excluding placement of vascular access) or minor surgery within 14 days of entry into the study,
* History of hypersensitivity to involved study drug(s) or of its excipients,
* Radiological evidence of symptomatic or progressive brain metastases,
* Participant with oral anticoagulation therapy,
* Inability to swallow,
* Major problem with intestinal absorption,
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Commissariat A L'energie Atomique

OTHER_GOV

Sponsor Role collaborator

Institut Bergonié

OTHER

Sponsor Role collaborator

Plateforme labellisée Inca - Institut Bergonié, Bordeaux

UNKNOWN

Sponsor Role collaborator

Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris

UNKNOWN

Sponsor Role collaborator

EUCLID Clinical Trial Platform

OTHER

Sponsor Role collaborator

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

OTHER_GOV

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Antoine Italiano

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Institut Bergonie

Bordeaux, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

Institut de Cancérologie de Montpellier

Montpellier, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Hôpital Pitié Salpétrière

Paris, , France

Site Status

Institut Curie

Paris, , France

Site Status

CHU Poitiers

Poitiers, , France

Site Status

Centre Eugène Marquis

Rennes, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, , France

Site Status

ICANS - Institut de Cancérologie Strasbourg

Strasbourg, , France

Site Status

IUCT Oncopôle

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 30523434 (View on PubMed)

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.

Reference Type RESULT
PMID: 32713836 (View on PubMed)

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.

Reference Type RESULT
PMID: 34740331 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024-514873-22-00

Identifier Type: CTIS

Identifier Source: secondary_id

2017-002851-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C16-40

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Trial of Dasatinib in Advanced Sarcomas
NCT00464620 COMPLETED PHASE2