NCT03784014

Molecular Profiling of Advanced Soft-tissue Sarcomas

Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 603 (actual)
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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

• Soft Tissue Sarcoma

Interventions

Type	Name	Description
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

Timeline

• Start date: 2019-10-19
• Primary completion: 2023-12-01
• Completion: 2026-01-13
• First posted: 2018-12-21
• Last updated: 2025-12-11

Locations

17 sites across 1 country: France