Interest of Post-operative Chemotherapy in Patients With Localised Uterine Leiomyosarcoma Suspected of Having a High Risk of Recurrence Based on a Biological Test Performed on the Tumour

Inclusion Criteria:

1. Patient must have a histologically confirmed diagnosis of uterine leiomyosarcomaobtained less than 8 weeks from the surgery

2. Eastern cooperative oncology group (ECOG) performance status (PS) 0 or 1

3. Patient was previously untreated with chemotherapy for a sarcoma, and did notreceive anthracyclines and/or trabectedin for another cancer

4. Available Formalin Fixed Paraffin Embedded (FFPE) tumor blocks in sufficientquantity and quality to allow CINSARC NanoCind® qualification (low-risk orhigh-risk)

5. Age ≥ 18 years and ≤ 75 years

6. FIGO 2018 classification stage I (IA and IB), with complete resection (totalhysterectomy and optional bilateral oophorectomy; possible ovarian preservation isfeasible in selected cases)

7. No measurable disease, as assessed by the investigator: normal post-operativethoracic, abdominal and pelvic CT-scan or normal MRI of abdomen and pelvis + normalchest CT performed within 4 weeks prior to inclusion or randomization in the study

8. Signed informed consent form prior to any trial specific procedures consistent withinternational conference on harmonisation - good clinical practice (ICH-GCP) andlocal legislation

9. Patient must be affiliated to a social security system or in possession ofequivalent private health insurance (according to local regulations forparticipation in clinical trials). Additional inclusion criteria for randomization

10. Inclusion criteria checked at study entry are all still met at the time ofrandomization

11. High-risk CINSARC signature

12. Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a local sarcomaexpert pathologist from RRePS (Sarcoma Pathology Reference Network from NETSARC +)locally or by the study central RRePS expert pathologist.

13. Adequate hematologic organ function:

• absolute neutrophil count ≥ 1.5 Giga/ L

• hemoglobin ≥ 9 g/dL

• platelets ≥ 100 Giga/L

14. Adequate renal function: serum creatinine ≤ 1.5 mg/dL (≤ 132.6 µmol/L) or calculatedcreatinine clearance ≥60 mL/min (by the Cockcroft and Gault formula)

15. Adequate liver function: total bilirubin ≤ upper limit of normal (ULN),transaminases ≤ 2.5 x ULN, alkaline phosphatases ≤ 1.5 x ULN

16. Adequate cardiac function: cardiac ultrasound and/or isotopic ventriculography,shortening fraction (SF) > 30%, Left Ventricular Ejection Fraction (LVEF) (perultrasound or scintigraphy) > 50%

17. Creatine phosphokinase (CPK) ≤ 2,5 x ULN

18. Albumin ≥ 25 g/L

19. Signed informed consent form for the randomized phase, consistent with ICH-GCP andlocal legislation.

Exclusion Criteria:

• Exclusion criteria:

1. All other histology types of uterine sarcoma (adenosarcoma, endometrialsarcoma, undifferentiated uterine sarcoma)

2. Prior or concurrent malignant disease diagnosed or treated in the last 5 yearsexcept for adequately treated in situ carcinoma of the cervix, basal orsquamous skin cell carcinoma, or in situ transitional bladder cell carcinoma

3. Planned pelvic post-operative radiation therapy

4. Metastatic or measurable disease on CT-Scan

5. Known hypersensitivity to doxorubicin or trabectedin or to any of theexcipients

6. Any contra-indication for the use of doxorubicin and/or trabectedin treatment

7. Participation in another therapeutic trial within the 30 days prior toinclusion in the study

8. Active viral hepatitis B or C or known human immunodeficiency virus (HIV)infection.

9. Prior anticancer therapy, including radiotherapy, endocrine therapy,immunotherapy, chemotherapy (CT) or other investigational agents within thelast 4 weeks (6 weeks for nitrosoureas and mitomycin C)

10. Cardiovascular dysfunction:

• Congestive heart failure (New York Heart Association [NYHA]) ≥ 2)

• Myocardial infarction <6 months before study

• Poorly controlled cardiac arrhythmias

• Uncontrolled hypertension

• Unstable (angina symptoms at rest) or new-onset angina (begun within the last 3months) 11. Ongoing infection > Grade 2 according to NCI-CTCAE v5.0 12.Breastfeeding woman 13. Patients unwilling or unable to comply with the medicalprocedures and follow-up required by the trial because of geographic, familial,social, or psychological reasons 14. Persons deprived of their liberty or underprotective custody or guardianship.

Additional exclusion criteria for randomization 15. At least one of the exclusion criteria check at study entry is met at the time of randomization 16. Unknown risk for CINSARC signature 17. For patients who require a pathological review by the study central pathologist, failure to obtain a confirmed diagnosis at randomization 18. More than 13 weeks have elapsed since the surgery procedure. 19. Patient receiving phenytoin within 88 hours prior to randomisation and or live attenuated vaccines within 14 days prior to randomisation and or CYP3A4 inhibitors (e.g. oral ketoconazole, fluconazole, ritonavir, clarithromycin or aprepitant) and or strong CYP3A4 inducers (e.g. rifampicin, phenobarbital, St John's wort).

Criteria for continuing in the prospective cohort :

1. Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a sarcomaexpert pathologist or by the study central pathologist

2. Patients with a low-risk CINSARC signature