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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-514873-22-00 | EU Trial (CTIS) Number | ||
| 2017-002851-27 | EudraCT Number |
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| Name | Class |
|---|---|
| Commissariat A L'energie Atomique | OTHER_GOV |
| Institut Bergonié | OTHER |
| Plateforme labellisée Inca - Institut Bergonié, Bordeaux | UNKNOWN |
| Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year progression-free survival (PFS) | PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first) | 1 year |
| Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year progression-free survival (PFS) |
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Randomized phase
Inclusion Criteria:
Exclusion Criteria:
Phase II Sub-trials
Inclusion Criteria:
Main exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Antoine Italiano | Institut Bergonié | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut Bergonie | Bordeaux | France | ||||
| Centre Georges François Leclerc |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30523434 | Background | 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. | |
| 32713836 | Result | 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. |
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Data from the MULTISARC study will be integrated into the Data Collector and Analyzer (CAD) provided for the Plan for Personalized Genomic Medicine 2025, where they will be stored for use in diagnostic and prognostic decision support, the development of therapeutic strategies, and health-related research, studies and evaluations.
Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of scientific and ethic commitee of the CAD.
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| UNKNOWN |
| EUCLID Clinical Trial Platform | OTHER |
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.
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| Next Generation sequencing exome | Other | Both frozentumor material (archived or newly obtained) and blood sample collection will be used for genetic profiling |
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PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first) |
| 2 years |
| Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year overall survival (OS) | OS will be defined as the delay from the date of randomization to the date of death (whatever the cause) | 1 year |
| Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year overall survival (OS) | OS will be defined as the delay from the date of randomization to the date of death (whatever the cause) | 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 | Delay from the date of signature of the informed consent to the date of the molecular tumor board | an average of 7 weeks |
| Assessment of the proportion of patients with Advanced STS presenting at least one targetable genomic alteration | A participant will be considered as "presenting at least one targetable genomic alteration", if the MTB considers that at least one genetic alteration identified can be matched with one of the drugs available through the MULTISARC study | An average of 7 weeks |
| Assessment of the efficacy of first-line systemic treatment in terms of 1-year progression-free survival | PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first) | 1 year |
| Assessment of the efficacy of first-line systemic treatment in terms of 2-year progression-free survival | PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first) | 2 years |
| Assessment of the efficacy of first-line systemic treatment in terms of 1-year overall survival | OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause). | 1 year |
| Assessment of the efficacy of first-line systemic treatment in terms of 2-year overall survival | OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause). | 2 years |
| Assessment of the efficacy of first-line systemic treatment in terms of best overall response under first-line treatment | Best response is recorded from the date of onset of first-line treatment until the end of first-line treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria | Throughout the treatment period, an average of 18 weeks |
| Assessment of the efficacy of first-line systemic treatment in terms of 6-month objective response | Objective response is defined as complete or partial response (CR, PR) as per RECIST v1.1 under first-line treatment | 6 months |
| Assessment of the efficacy of first-line systemic treatment in terms of 6-month non progression | Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under first-line treatment as defined as per RECIST v1.1 | 6 months |
| Assessment of the efficacy of each targeted treatment in terms of 6-month non progression | Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under targeted treatment as defined as per RECIST v1.1 | 6 months |
| Assessment of the efficacy of each targeted treatment in terms of 1-year progression-free survival | PFS will be defined as the delay from the date of targeted treatment initiation to the date of progression as per RECIST v1.1 or death, whichever occurs first | 1 year |
| Assessment of the efficacy of each targeted treatment in terms of 1-year overall survival | OS is defined as the delay from the date of targeted treatment initiation to the date of death (whatever the cause) | 1 year |
| Assessment of the efficacy of each targeted treatment in terms of best overall response under treatment | Best response (partial or complete, as per RECIST v1.1) recorded from date of targeted treatment initiation taking into account any requirement for confirmation as per RECIST v1.1 criteria | Throughout the treatment period, an average of 6 months |
| Assessment of the efficacy of each targeted treatment in terms of objective response under treatment | Complete response or partial response under targeted treatment as defined as per RECIST evaluation criteria v1.1 | Throughout the treatment period, an average of 6 months |
| Assessment of the efficacy of each targeted treatment in terms of change in tumor size (CTS) | CTS is defined as the difference (in percentage) in tumor size burden from the date of targeted treatment initiation (baseline) to the tumor assessment | Throughout the treatment period, an average of 6 months |
| Assessment of the safety profile of each targeted treatment using the CTCAE v5 | Safety will be assessed as per CTCAE v5 | Throughout the treatment period, an average of 6 months |
| Impact of the results of immunosequencing during first-line treatment | Correlation of TCR-sequencing data with objective response (OR), OR), progression-free survival (PFS) and overall survival (OS). Evaluation of the association between immune profiles derived from ancillary analyses (VISIUM HD, multiplex IF, SomaScan proteomics) and treatment response, within an integrated immunosequencing framework. | At cycle 2 day 1 of targeted treatment |
| To estimate the cost-effectiveness of the strategy usdin NGS as compared to the strategy without NGS | The outcome will be the incremental cost-utility ratio or the incremental cost per incremental Quality Adjusted Life Year (QALY) | Trhoughout the study period, an average of 2 years |
| To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results | Proportion of participants with interpretable NGS results | an average of 7 weeks |
| To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of delays | Delay from the date of treatment failure (progression, investigator decision, end of last treatment line) to the date of the molecular tumor board | an average of 7 weeks |
| To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results | Proportion of participants presenting at least one targetable genomic alteration | an average of 7 weeks |
| Dijon |
| France |
| Centre Oscar Lambret | Lille | France |
| Centre Léon Bérard | Lyon | France |
| Institut Paoli Calmettes | Marseille | France |
| Institut de Cancérologie de Montpellier | Montpellier | France |
| Centre Antoine Lacassagne | Nice | France |
| Hôpital Cochin | Paris | France |
| Hôpital Pitié Salpétrière | Paris | France |
| Institut Curie | Paris | France |
| CHU Poitiers | Poitiers | 86000 | France |
| Centre Eugène Marquis | Rennes | 35042 | France |
| Centre Henri Becquerel | Rouen | France |
| Institut de Cancérologie de l'Ouest - Site René Gauducheau | Saint-Herblain | France |
| ICANS - Institut de Cancérologie Strasbourg | Strasbourg | 67033 | France |
| IUCT Oncopôle | Toulouse | France |
| Institut Gustave Roussy | Villejuif | France |
| 34740331 | 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. |
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C498826 | nilotinib |
| C586847 | ceritinib |
| C000613976 | capmatinib |
| D000077341 | Lapatinib |
| C560077 | trametinib |
| C561627 | dabrafenib |
| C531550 | olaparib |
| C000613593 | durvalumab |
| C500026 | palbociclib |
| C000592580 | glasdegib |
| C000713257 | futibatinib |
| D001483 | Base Sequence |
| D059014 | High-Throughput Nucleotide Sequencing |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D015394 | Molecular Structure |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
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