Adult patients with locally advanced/unresectable and/or metastatic soft-tissue sarcoma MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10039494 Term: Sarcoma NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps
Conditions
Interventions
Trade Name: TASIGNA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Other descriptive name: AMN107
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
INSERM
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years, 2) Histology: soft-tissue sarcoma confirmed by the RRePS Network, as recommended by the French NCI, 3) Metastatic STS, 4) No previous systemic treatment for metastatic disease, 5) Eastern Cooperative Oncology Group (ECOG) performance status = 1, 6) Adequate hematological and metabolic functions: a. Hemoglobin = 9 g/dl b. Albumin = 30 g/dl 7) Measurable disease according to RECIST 1.1. At least one site of disease must be uni-dimensionally > 10 mm, 8) Availability of suitable frozen archive tumor material from a metastatic or advanced disease (not previously treated), 9) Archived FFPE block of specimen tumor sampling obtained anytime during disease development for research purpose, 10) Eligible to first-line standard chemotherapy regimen, 11) No prior or concurrent malignant disease diagnosed or treated in the last two years before inclusion, except for in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of the skin and prostate cancer, 12) Patient with a social security in compliance with the French law, 13) Voluntary signed and dated written informed consent prior to any study specific procedure (ICF1). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 768 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: 1) Radiological evidence of symptomatic or progressive brain metastases, 2) Inability to swallow, 3) Major problem with intestinal absorption, 4) Previous allogeneic bone marrow transplant, 5) Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV or active autoimmune disease), 6) 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, 7) Individuals deprived of liberty or placed under guardianship 8) Pregnant or breast feeding women, 9) Men or women refusing contraception, 10) Previous enrolment in the present study, 11) Any contraindication to first-line chemotherapy treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In patients with advanced STS: to assess the feasibility of high throughput molecular analysis (next generation sequencing exome [NGS]). - Primary objective will be assessed in patients randomized in the arm “NGS”. - Feasibility will be defined as the proportion of patients 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.;Secondary Objective: 1) Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of: - Progression-free survival (median PFS, PFS after 1- and 2-year follow-up), - Overall survival (median OS, OS after 1- and 2-year follow-up). 2) Assessment of the feasibility of high throughput molecular analysis NGS (exome, RNASeq) in terms of additional feasibility endpoints: - Proportion of patients with interpretable NGS results - For patients with interpretable NGS: results delay from the date of signature of the informed consent to the date of the molecular tumor board. 3) Assessment of the proportion of patients with advanced STS presenting at least one targetable genomic alteration. 4) Assessment of the efficacy of first-line anthracycline-based chemotherapy. 5) Assessment of the efficacy and the safety profile of each targeted treatment. 6) Assessment of the cost-effectiveness of the NGS strategy (vs. no NGS). 7) Impact of the result of immunosequencing on OR, PFS and OS.;Primary end point(s): - Feasibility of high throughput molecular analysis (next generation sequencing exome, NGS) NGS (exome) will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a molecular tumor board is provided to investigators within 7 weeks from reception of the samples by o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): EFFICACY ENDPOINTS - Efficacy of an innovative treatment strategy guided by high throughput molecular analysis (next generation exome sequencing, RNASeq [NGS], immunological profiling) in participants with advanced soft-tissue sarcomas [STS] * Overall survival (OS): OS is defined as the delay from the date of randomization to the date of death (whatever the cause). * 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. - Participants with targetable alteration(s) 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. - Efficacy of first-line anthracycline-based chemotherapy (in all participants) * OS * PFS * Best response: best response 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 * 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-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 - Efficacy of each targeted treatment * Following RECIST v1.1 recommendation, each participant will be assigned one of the following categories: complete response, partial response, stable disease, progression, invaluable for response * 6-month non-progression * OS * PFS * Best response * Objective response * 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. SAFETY ENDPOINTS For STS parti | — |
Countries
France
Contacts
Public ContactHélène ESPEROU
INSERM
Outcome results
None listed