Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma

Inclusion Criteria: 1. Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network 2. According to FNCLCC grading system, grade 1, 2 or 3 tumors 3. Resectable and localized disease after appropriate extension work-up (including at least a chest-CT) 4. 6 weeks or less between surgical excision and inclusion (if performed before inclusion) 5. Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification 6. Age ≥ 18 years 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 8. Life expectancy of at least 12 weeks after the start of the treatment 9. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period and at least 12 months (ifosfamide treatment) or 6 months (dacarbazine treatment) after the end of the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to registration. Men should accept to use an effective contraception during treatment period and at least 3 months after the end of the study treatment. 10. Signed written informed consent 11. Patient affiliated to a Social Health Insurance in France. Exclusion Criteria: 1. Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcomas, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, epithelioid sarcoma, alveolar or embryonal rhabdomyosarcoma 2. Primitive cutaneous, retroperitoneal, uterus or visceral STS 3. Metastatic disease 4. Previous or ongoing treatment for the sarcoma (with the exception of surgical excision) 5. Contra-indication for Doxorubicin, Ifosfamide and Dacarbazine treatments 6. Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards, and prior therapy with anthracyclines 7. Prior mediastinal/cardiac radiotherapy 8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, myocardial infarction within 6 months prior to study entry 9. Prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma 10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 11. Known infection with HIV, hepatitis B, or hepatitis C 12. Women who are breastfeeding, pregnant or who plan to become pregnant while in the trial 13. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study 14. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice) 15. Patient unable to comply with the protocol for any reason. ADDITIONAL CRITERIA FOR THE RANDOMIZED PHASE III STUDY 1. High-risk CINSARC signature 2. Acceptable hematologic function (within 72 hours prior randomization): Absolute neutrophil count (ANC) ≥ 1.5 G/L, Platelet count ≥ 100 G/L and Hemoglobin \> 9g/dL 3. Acceptable renal function within 72 hours prior randomization: Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (by the Cockcroft and Gault formula) 4. Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN 5. Normal LVEF (\>50%) measured by echocardiography or isotopic ventriculography