TRABECTEDIN for Uterine leiomyosarcoma

Inclusion criteria

• {"criterion_text":"- Patient must have a histologically confirmed diagnosis of uterine leiomyosarcoma obtained less than 8 weeks from the surgery\n- For randomization : Inclusion criteria checked at study entry are all still met at the time of randomization\n- For randomization : High-risk CINSARC signature\n- 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.\n- For randomization : Adequate hematologic organ function: - absolute neutrophil count ≥ 1.5 Giga/ L - hemoglobin ≥ 9 g/dL - platelets ≥ 100 Giga/L\n- 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)\n- For randomization : Adequate liver function: total bilirubin ≤ ULN, transaminases ≤ 2.5 x ULN, alkaline phosphatases ≤ 1.5 x ULN\n- 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%\n- For randomization : Creatine phosphokinase (CPK) ≤ 2,5 x ULN\n- For randomization : Albumin ≥ 25 g/L\n- For randomization : Signed informed consent form for the randomized phase, consistent with ICH-GCP and local legislation.\n- ECOG performance status (PS) 0 or 1\n- Patient was previously untreated with chemotherapy for a sarcoma, and did not receive anthracyclines and/or trabectedin for another cancer\n- 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)\n- Age ≥ 18 years and ≤ 75 years\n- 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)\n- 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\n- Signed informed consent form prior to any trial specific procedures consistent with ICHGCP and local legislation\n- 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

• {"criterion_text":"- All other histology types of uterine sarcoma (adenosarcoma, endometrial sarcoma, undifferentiated uterine sarcoma)\n- For randomization : More than 13 weeks have elapsed since the surgery procedure.\n- 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\n- Planned pelvic post-operative radiation therapy\n- Metastatic or measurable disease on CT-Scan\n- Known hypersensitivity to doxorubicin or trabectedin or to any of the excipients\n- Any contra-indication for the use of doxorubicin and/or trabectedin treatment\n- Participation in another therapeutic trial within the 30 days prior to inclusion in the study\n- Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection.\n- 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)\n- 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).\n- 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)\n- Ongoing infection > Grade 2 according to NCI-CTCAE v5.0\n- Breastfeeding woman\n- 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\n- Persons deprived of their liberty or under protective custody or guardianship.\n- For randomization : At least one of the exclusion criteria check at study entry is met at the time of randomization\n- For randomization : Unknown risk for CINSARC signature\n- For randomization : For patients who require a pathological review by the study central pathologist, failure to obtain a confirmed diagnosis at randomization"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the RFS, which is defined as the time from the date of randomization assignment to the date of first disease recurrence/relapse (local/regional recurrence and/or distant metastasis) or death from any cause whichever comes first. Patients still alive at the time of analysis (including lost to follow-up) without appearance of relapse or recurrence will be censored at the last disease assessment date.","definition_or_measurement_approach":"RFS defined as time from randomization to first disease recurrence/relapse (local/regional and/or distant metastasis) or death from any cause; patients alive without relapse at analysis are censored at last disease assessment date."}

Secondary endpoints

• {"endpoint_text":"- Randomized part : Overall survival (OS) is defined by the time between randomization and death from any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; alive patients censored at last known alive date."}
• {"endpoint_text":"- Randomized part : Metastases-free survival (MFS) is defined by the time between randomization and the appearance of metastatic disease or death from any cause. In case of initial loco-regional relapse, patients will be censored at the date of appearance. Patients still alive at the time of analysis (including lost to follow-up) without appearance of metastatic disease will be censored at the last disease assessment date.","definition_or_measurement_approach":"MFS defined as time from randomization to metastatic disease appearance or death; initial loco-regional relapse leads to censoring at date of appearance; alive without metastasis censored at last disease assessment date."}
• {"endpoint_text":"- Randomized part : Safety and tolerability (NCI-CTCAE v5.0) will be assessed through the incidence of adverse events, treatment-related adverse events, serious adverse events (SAEs) and death.","definition_or_measurement_approach":"Safety assessed by incidence of AEs, treatment-related AEs, SAEs and deaths graded per NCI-CTCAE v5.0."}
• {"endpoint_text":"- Randomized part : Quality of life (QoL) will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. A deterioration of scores for five-targeted dimensions: pain, physical and emotional functioning, fatigue, and appetite will be compared between the two treatment arms, while other dimensions will be regarded as exploratory.","definition_or_measurement_approach":"QoL measured with EORTC QLQ-C30; deterioration in pain, physical and emotional functioning, fatigue, and appetite compared between arms; other domains exploratory."}
• {"endpoint_text":"- Prognostic value : The RFS is defined as the time from the date of inclusion assignment to the date of first disease recurrence/relapse (local/regional recurrence and/or distant metastasis) or death from any cause, whichever comes first. Patients still alive at the time of analysis (including lost to followup) without appearance of relapse or recurrence will be censored at the last disease assessment date.","definition_or_measurement_approach":"Prognostic RFS defined as time from inclusion to first recurrence/relapse or death; alive without relapse censored at last assessment."}
• {"endpoint_text":"- Prognostic value : Overall survival (OS) is defined by the time between inclusion and death from any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.","definition_or_measurement_approach":"Prognostic OS defined as time from inclusion to death from any cause; alive censored at last known alive date."}
• {"endpoint_text":"- Prognostic value : Metastases-free survival (MFS) is defined by the time between inclusion and the appearance of metastatic disease or death from any cause. In case of initial loco-regional relapse, patients will be censored at the date of appearance. Patients still alive at the time of analysis (including lost to follow-up) without appearance of metastatic disease will be censored at the last disease assessment date.","definition_or_measurement_approach":"Prognostic MFS defined as time from inclusion to metastatic disease appearance or death; initial loco-regional relapse censored at appearance; alive without metastasis censored at last disease assessment date."}

France

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

25-03-2025

Processing Time Days

273

Number Of Sites

29

Number Of Participants

198

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France