Leiomyosarcoma Uterus
Conditions
Brief summary
Addition of postoperative chemotherapy to prevent or delay recurrence in patients newly diagnosed with localized uterine leiomyosarcoma and who have undergone complete tumor surgery.
Detailed description
This is a biological driven study comprising: * a multicenter, randomized and comparative phase II trial designed to demonstrate whether adding 4 cycles of post-operative chemotherapy improves relapse-free survival as compared with follow-up (standard management) in patients with resected FIGO stage I uterine leiomyosarcoma, considered at high-risk according to CINSARC NanoCind® signature. * a prospective cohort for patients with resected FIGO stage I uterine leiomyosarcoma, considered at low-risk according to CINSARC NanoCind® signature. HIGH-RISK (HR) CINSARC patients will be randomized post-operatively between the two arms of treatment, i.e. standard treatment (active post-surgical surveillance) or chemotherapy, with a 1:1 randomization on one factor: morcellation versus no morcellation of uterine tumor. LOW-RISK (LR) CINSARC patients' data will be prospectively collected
Interventions
DRUGDoxorubicin
60 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
DRUGTrabectedin
1.1 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
Sponsors
PharmaMar
Ligue contre le cancer, France
National Research Agency, France
University Hospital, Marseille
Institut Claudius Regaud
Institut Bergonié
Oncopole
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Multicenter, randomized and comparative phase II trial and prospective cohort
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patient must have a histologically confirmed diagnosis of uterine leiomyosarcoma obtained 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 not receive anthracyclines and/or trabectedin for another cancer 4. Available Formalin Fixed Paraffin Embedded (FFPE) tumor blocks in sufficient quantity and quality to allow CINSARC NanoCind® qualification (low-risk or high-risk) 5. Age ≥ 18 years and ≤ 75 years 6. 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) 7. 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 8. Signed informed consent form prior to any trial specific procedures consistent with international conference on harmonisation - good clinical practice (ICH-GCP) and local legislation 9. 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). Additional inclusion criteria for randomization 10. Inclusion criteria checked at study entry are all still met at the time of randomization 11. High-risk CINSARC signature 12. Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a local sarcoma expert 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 calculated creatinine 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) (per ultrasound 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 and local legislation.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free survival | From randomization or enrollment to disease recurrence or death, up to 5 years | The relapse-free survival is defined as the time from the date of randomization assignment (or the date of enrollment for patients in the prospective cohort) to the date of first disease recurrence/relapse (local/regional recurrence and/or distant metastasis) or death from any cause whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From randomization or enrollment to death, up to 5 years | The overall survival is the length of time from randomization (or enrollment for patients in the prospective cohort) that patients enrolled in the study are still alive. |
| Metastases-free survival | From randomization or enrollment to metastases onset or death, up to 5 years | The metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. |
| Incidence of adverse events | Throughout study completion, up to 5 years | The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = death) determined by the investigator, will make it possible to assess the severity of the disorders. 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. |
| Quality of life questionnaire - Core 30 (QLQ-C30) | At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years | Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
Countries
France
Contacts
Primary ContactAmel MEKALICHE, MS
Outcome results
None listed