Interest of post-operative chemotherapy in patients with localized uterine leiomyosarcoma suspected to have a high-risk of relapse based on a biologic test performed on the tumor.

Phase 1

• Conditions: ocalized, resected, FIGO stage I (2018 classification), uterine leiomyosarcoma; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-506350-21-00
• Lead Sponsor: nicancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-12
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 198

Inclusion Criteria

Patient must have a histologically confirmed diagnosis of uterine leiomyosarcoma obtained less than 8 weeks from the surgery, For randomization : Inclusion criteria checked at study entry are all still met at the time of randomization, For randomization : High-risk CINSARC signature, For randomization : Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a local sarcoma expert pathologist from RRePS (Sarcoma Pathology Refernce Netword from NETSARC +) locally or by the study central RRePS expert pathologist., For randomization : Adequate hematologic organ function: - absolute neutrophil count = 1.5 Giga/ L - hemoglobin = 9 g/dL - platelets = 100 Giga/L, For randomization : Adequate renal function: serum creatinine = 1.5 mg/dL (= 132.6 µmol/L) or calculated creatinine clearance =60 mL/min (by the Cockcroft and Gault formula), For randomization : Adequate liver function: total bilirubin = ULN, transaminases = 2.5 x ULN, alkaline phosphatases = 1.5 x ULN, For randomization : Adequate cardiac function: cardiac ultrasound and/or isotopic ventriculography, shortening fraction (SF) > 30%, Left Ventricular Ejection Fraction (LVEF) (per ultrasound or scintigraphy) > 50%, For randomization : Creatine phosphokinase (CPK) = 2,5 x ULN, For randomization : Albumin = 25 g/L, For randomization : Signed informed consent form for the randomized phase, consistent with ICH-GCP and local legislation., ECOG performance status (PS) 0 or 1, Patient was previously untreated with chemotherapy for a sarcoma, and did not receive anthracyclines and/or trabectedin for another cancer, Available Formalin Fixed Paraffin Embedded (FFPE) tumor blocks in sufficient quantity and quality to allow CINSARC NanoCind® qualification (low-risk or high-risk) (1 block), Age = 18 years and = 75 years, FIGO 2018 classification stage I (IA and IB), with complete resection (total hysterectomy and optional bilateral oophorectomy; possible ovarian preservation is feasible in selected cases), No measurable disease, as assessed by the investigator: normal post-operative thoracic, abdominal and pelvic CT scan or normal MRI of abdomen and pelvis + normal chest CT performed within 4 weeks prior to inclusion or randomization in the study, Signed informed consent form prior to any trial specific procedures consistent with ICHGCP and local legislation, Patient must be affiliated to a social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).

Exclusion Criteria

All other histology types of uterine sarcoma (adenosarcoma, endometrial sarcoma, undifferentiated uterine sarcoma), For randomization : More than 13 weeks have elapsed since the surgery procedure., Prior or concurrent malignant disease diagnosed or treated in the last 5 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma, Planned pelvic post-operative radiation therapy, Metastatic or measurable disease on CT-Scan, Known hypersensitivity to doxorubicin or trabectedin or to any of the excipients, Any contra-indication for the use of doxorubicin and/or trabectedin treatment, Participation in another therapeutic trial within the 30 days prior to inclusion in the study, Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection., Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) or other investigational agents within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C), 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)., 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 3 months), Ongoing infection > Grade 2 according to NCI-CTCAE v5.0, Breastfeeding woman, Patients unwilling or unable to comply with the medical procedures and follow-up required by the trial because of geographic, familial, social, or psychological reasons, Persons deprived of their liberty or under protective custody or guardianship., For randomization : At least one of the exclusion criteria check at study entry is met at the time of randomization, For randomization : Unknown risk for CINSARC signature, For randomization : For patients who require a pathological review by the study central pathologist, failure to obtain a confirmed diagnosis at randomization

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified