Interesse della chemioterapia postoperatoria in pazienti con leiomiosarcoma uterino localizzato sospettato di avere un alto rischio di recidiva sulla base di un test biologico eseguito sul tumore (L-UteCIN)
Interesse della chemioterapia adiuvante nei pazienti con leiomiosarcoma uterino resecato localizzato ad alto rischio CINSARC - Sarcome 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Contatto studio
- Nome: Amel MEKALICHE, MS
- Numero di telefono: +33 761947045
- Email: a-mekaliche@unicancer.fr
Luoghi di studio
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Angers, Francia, 49100
- Non ancora reclutamento
- Institut de Cancerologie de L'Ouest (Ico)
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Investigatore principale:
- Patrick SOULIÉ, MD
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Besançon, Francia, 25030
- Non ancora reclutamento
- Hopital Jean Minjoz
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Investigatore principale:
- Loic CHAIGNEAU, MD
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Bordeaux, Francia, 33076
- Non ancora reclutamento
- Institut Bergonie
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Investigatore principale:
- Maud TOULMONDE, MD
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Caen, Francia, 14176
- Non ancora reclutamento
- Centre Francois Baclesse
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Investigatore principale:
- Zoé NEVIERE, MD
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Clermont-Ferrand, Francia, 63011
- Non ancora reclutamento
- Centre Jean Perrin
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Investigatore principale:
- Pascale DUBRAY-LONGERAS, MD
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Dijon, Francia, 21079
- Non ancora reclutamento
- Centre Georges Francois Leclerc
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Investigatore principale:
- Isabelle DESMOULINS, MD
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Limoges, Francia, 87042
- Non ancora reclutamento
- Chu Limoges
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Investigatore principale:
- Tiffany DARBAS, MD
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Lyon, Francia, 69373
- Non ancora reclutamento
- Centre Léon Berard
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Investigatore principale:
- Isabelle RAY-COCUARD, MD PhD
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Marseille, Francia, 13273
- Non ancora reclutamento
- Institut Paoli Calmettes
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Investigatore principale:
- François BERTUCCI, MD PhD
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Marseille, Francia, 13385
- Reclutamento
- La Timone University Hospital
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Investigatore principale:
- Florence DUFFAUD, MD PhD
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Nice, Francia, 06189
- Non ancora reclutamento
- Centre Antoine Lacassagne
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Investigatore principale:
- Agnès DUCOULOMBIER, MD
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Paris, Francia, 75014
- Non ancora reclutamento
- Hôpital Cochin
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Investigatore principale:
- Sixtine DE PERCIN, MD
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Paris, Francia
- Non ancora reclutamento
- Institut Curie
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Investigatore principale:
- Clément BONET, MD
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Paris, Francia, 75010
- Non ancora reclutamento
- Hopital Saint Louis
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Investigatore principale:
- Tiphaine LAMBERT, MD
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Paris, Francia, 75020
- Non ancora reclutamento
- Groupe Hospitalier Diaconesses Croix St Simon
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Investigatore principale:
- Frédéric SELLE, MD
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Paris, Francia, 75020
- Non ancora reclutamento
- Hopital Tenon
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Investigatore principale:
- Laurent SEKNAZI, MD
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Poitiers, Francia, 86000
- Non ancora reclutamento
- Chu de Poitiers
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Investigatore principale:
- Nicolas ISAMBERT, MD PHD
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Rennes, Francia, 35042
- Non ancora reclutamento
- Centre Eugene Marquis
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Investigatore principale:
- Christophe PERRIN, MD
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Rouen, Francia, 76038
- Non ancora reclutamento
- Centre Henri Becquerel
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Investigatore principale:
- Cécile GUILLEMET, MD
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Saint-Herblain, Francia, 44805
- Non ancora reclutamento
- Institut de cancerologie de l'ouest site Rene Gauducheau
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Investigatore principale:
- Pierre KUBICEK, MD
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Strasbourg, Francia
- Non ancora reclutamento
- Institut de Cancerologie Strasbourg Europe (Icans)
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Contatto:
- Jean-Emmanuel KURTZ, MD
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Toulouse, Francia, 31052
- Non ancora reclutamento
- Institut Claudius Regaud
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Investigatore principale:
- Thibaud VALENTIN, MD
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Tours, Francia, 37000
- Non ancora reclutamento
- CHU Bretonneau
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Investigatore principale:
- Mathilde CANCEL, MD
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Vandœuvre-lès-Nancy, Francia, 54519
- Non ancora reclutamento
- Centre Alexis Vautrin
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Investigatore principale:
- Maria RIOS, MD
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Villejuif, Francia, 94800
- Reclutamento
- Gustave Roussy
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Investigatore principale:
- Patricia PAUTIER, MD
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Nessun intervento: Arm A
Standard of care : Active surveillance |
|
|
Sperimentale: 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)
Altri nomi:
|
|
Nessun intervento: Prospective Cohort
Standard of care : Active surveillance |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Relapse-free survival
Lasso di tempo: 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. |
From randomization or enrollment to disease recurrence or death, up to 5 years
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Overall survival
Lasso di tempo: 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. |
From randomization or enrollment to death, up to 5 years
|
|
Metastases-free survival
Lasso di tempo: 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. |
From randomization or enrollment to metastases onset or death, up to 5 years
|
|
Incidence of adverse events
Lasso di tempo: 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. |
Throughout study completion, up to 5 years
|
|
Quality of life questionnaire - Core 30 (QLQ-C30)
Lasso di tempo: 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. |
At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Florence DUFFAUD, MD, La TIMONE University Hospital
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Prodotti chimici organici
- Composti eterociclici, 1-anello
- Composti eterociclici
- Composti eterociclici, 2 anelli
- Composti eterociclici, anello fuso
- Idrocarburi
- Idrocarburi, ciclici
- Carboidrati
- Idrocarburi policiclici aromatici
- Idrocarburi, aromatici
- Composti policiclici
- Glicosidi
- Antracicline
- Naftaceni
- Aminoglicosidi
- Daunorubicina
- Diossole
- Tetraidroisochinoline
- Isochinolinine
- Trabectedina
- Doxorubicina
Altri numeri di identificazione dello studio
- UC-SAR-2212
- 2023-506350-21-00 (Ctis)
- 2023 (Sovvenzione/contratto NIH degli Stati Uniti)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano 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.
Informazioni su farmaci e dispositivi, documenti di studio
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