Interés de la quimioterapia posoperatoria en pacientes con leiomiosarcoma uterino localizado con sospecha de alto riesgo de recurrencia según una prueba biológica realizada al tumor (L-UteCIN)
Interés de la quimioterapia adyuvante en pacientes con leiomiosarcoma uterino resecado localizado de alto riesgo CINSARC - Sarcoma 15
Addition of postoperative chemotherapy to prevent or delay recurrence in patients newly diagnosed with localized uterine leiomyosarcoma and who have undergone complete tumor surgery.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Amel MEKALICHE, MS
- Número de teléfono: +33 761947045
- Correo electrónico: a-mekaliche@unicancer.fr
Ubicaciones de estudio
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Angers, Francia, 49100
- Aún no reclutando
- Institut de Cancerologie de L'Ouest (Ico)
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Investigador principal:
- Patrick SOULIÉ, MD
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Besançon, Francia, 25030
- Aún no reclutando
- Hopital Jean Minjoz
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Investigador principal:
- Loic CHAIGNEAU, MD
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Bordeaux, Francia, 33076
- Aún no reclutando
- Institut Bergonie
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Investigador principal:
- Maud TOULMONDE, MD
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Caen, Francia, 14176
- Aún no reclutando
- Centre Francois Baclesse
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Investigador principal:
- Zoé NEVIERE, MD
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Clermont-Ferrand, Francia, 63011
- Aún no reclutando
- Centre Jean Perrin
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Investigador principal:
- Pascale DUBRAY-LONGERAS, MD
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Dijon, Francia, 21079
- Aún no reclutando
- Centre Georges Francois Leclerc
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Investigador principal:
- Isabelle DESMOULINS, MD
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Limoges, Francia, 87042
- Aún no reclutando
- Chu Limoges
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Investigador principal:
- Tiffany DARBAS, MD
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Lyon, Francia, 69373
- Aún no reclutando
- Centre Léon Berard
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Investigador principal:
- Isabelle RAY-COCUARD, MD PhD
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Marseille, Francia, 13273
- Aún no reclutando
- Institut Paoli Calmettes
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Investigador principal:
- François BERTUCCI, MD PhD
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Marseille, Francia, 13385
- Reclutamiento
- La Timone University Hospital
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Investigador principal:
- Florence DUFFAUD, MD PhD
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Nice, Francia, 06189
- Aún no reclutando
- Centre Antoine Lacassagne
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Investigador principal:
- Agnès DUCOULOMBIER, MD
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Paris, Francia, 75014
- Aún no reclutando
- Hôpital Cochin
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Investigador principal:
- Sixtine DE PERCIN, MD
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Paris, Francia
- Aún no reclutando
- Institut Curie
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Investigador principal:
- Clément BONET, MD
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Paris, Francia, 75010
- Aún no reclutando
- Hopital Saint Louis
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Investigador principal:
- Tiphaine LAMBERT, MD
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Paris, Francia, 75020
- Aún no reclutando
- Groupe Hospitalier Diaconesses Croix St Simon
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Investigador principal:
- Frédéric SELLE, MD
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Paris, Francia, 75020
- Aún no reclutando
- Hopital Tenon
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Investigador principal:
- Laurent SEKNAZI, MD
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Poitiers, Francia, 86000
- Aún no reclutando
- Chu de Poitiers
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Investigador principal:
- Nicolas ISAMBERT, MD PHD
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Rennes, Francia, 35042
- Aún no reclutando
- Centre Eugene Marquis
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Investigador principal:
- Christophe PERRIN, MD
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Rouen, Francia, 76038
- Aún no reclutando
- Centre Henri Becquerel
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Investigador principal:
- Cécile GUILLEMET, MD
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Saint-Herblain, Francia, 44805
- Aún no reclutando
- Institut de cancerologie de l'ouest site Rene Gauducheau
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Investigador principal:
- Pierre KUBICEK, MD
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Strasbourg, Francia
- Aún no reclutando
- Institut de Cancerologie Strasbourg Europe (Icans)
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Contacto:
- Jean-Emmanuel KURTZ, MD
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Toulouse, Francia, 31052
- Aún no reclutando
- Institut Claudius Regaud
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Investigador principal:
- Thibaud VALENTIN, MD
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Tours, Francia, 37000
- Aún no reclutando
- CHU Bretonneau
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Investigador principal:
- Mathilde CANCEL, MD
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Vandœuvre-lès-Nancy, Francia, 54519
- Aún no reclutando
- Centre Alexis Vautrin
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Investigador principal:
- Maria RIOS, MD
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Villejuif, Francia, 94800
- Reclutamiento
- Gustave Roussy
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Investigador principal:
- Patricia PAUTIER, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Patient must have a histologically confirmed diagnosis of uterine leiomyosarcoma obtained less than 8 weeks from the surgery
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Eastern cooperative oncology group (ECOG) performance status (PS) 0 or 1
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Patient was previously untreated with chemotherapy for a sarcoma, and did not receive anthracyclines and/or trabectedin for another cancer
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Available Formalin Fixed Paraffin Embedded (FFPE) tumor blocks in sufficient quantity and quality to allow CINSARC NanoCind® qualification (low-risk or high-risk)
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Age ≥ 18 years and ≤ 75 years
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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)
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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
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Signed informed consent form prior to any trial specific procedures consistent with international conference on harmonisation - good clinical practice (ICH-GCP) and local legislation
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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
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Inclusion criteria checked at study entry are all still met at the time of randomization
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High-risk CINSARC signature
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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.
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Adequate hematologic organ function:
- absolute neutrophil count ≥ 1.5 Giga/ L
- hemoglobin ≥ 9 g/dL
- platelets ≥ 100 Giga/L
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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)
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Adequate liver function: total bilirubin ≤ upper limit of normal (ULN), transaminases ≤ 2.5 x ULN, alkaline phosphatases ≤ 1.5 x ULN
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Adequate cardiac function: cardiac ultrasound and/or isotopic ventriculography, shortening fraction (SF) > 30%, Left Ventricular Ejection Fraction (LVEF) (per ultrasound or scintigraphy) > 50%
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Creatine phosphokinase (CPK) ≤ 2,5 x ULN
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Albumin ≥ 25 g/L
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Signed informed consent form for the randomized phase, consistent with ICH-GCP and local legislation.
Exclusion Criteria:
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Exclusion criteria:
- All other histology types of uterine sarcoma (adenosarcoma, endometrial sarcoma, undifferentiated uterine sarcoma)
- 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)
- Cardiovascular dysfunction:
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Congestive heart failure (New York Heart Association [NYHA]) ≥ 2)
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Myocardial infarction <6 months before study
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Poorly controlled cardiac arrhythmias
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Uncontrolled hypertension
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Unstable (angina symptoms at rest) or new-onset angina (begun within the last 3 months) 11. Ongoing infection > Grade 2 according to NCI-CTCAE v5.0 12. Breastfeeding woman 13. 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 14. Persons deprived of their liberty or under protective 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 :
- Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a sarcoma expert pathologist or by the study central pathologist
- Patients with a low-risk CINSARC signature
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Sin intervención: Arm A
Standard of care : Active surveillance |
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Experimental: Arm B
Experimental treatment: 4 cycle of Doxorubicine + trabectedin |
60 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles) 1.1 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
Otros nombres:
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Sin intervención: Prospective Cohort
Standard of care : Active surveillance |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Relapse-free survival
Periodo de tiempo: From randomization or enrollment to disease recurrence or death, up to 5 years
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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. |
From randomization or enrollment to disease recurrence or death, up to 5 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Overall survival
Periodo de tiempo: From randomization or enrollment to death, up to 5 years
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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. |
From randomization or enrollment to death, up to 5 years
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Metastases-free survival
Periodo de tiempo: From randomization or enrollment to metastases onset or death, up to 5 years
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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. |
From randomization or enrollment to metastases onset or death, up to 5 years
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Incidence of adverse events
Periodo de tiempo: Throughout study completion, up to 5 years
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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. |
Throughout study completion, up to 5 years
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Quality of life questionnaire - Core 30 (QLQ-C30)
Periodo de tiempo: At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years
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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. |
At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Florence DUFFAUD, MD, La TIMONE University Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Hidrocarburos
- Hidrocarburos, cíclico
- Carbohidratos
- Hidrocarburos aromáticos policíclicos
- Hidrocarburos, aromáticos
- Compuestos policíclicos
- Glucósidos
- Antraciclinas
- Naftacenos
- Aminoglucósidos
- Daunorrubicina
- Dioxoles
- Tetrahidroisoquinolina
- Isoquinolinas
- Trabectedina
- Doxorrubicina
Otros números de identificación del estudio
- UC-SAR-2212
- 2023-506350-21-00 (Ctis)
- 2023 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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