Interessen for postoperativ kjemoterapi hos pasienter med lokalisert uterint leiomyosarkom mistenkt for å ha høy risiko for tilbakefall basert på en biologisk test utført på svulsten (L-UteCIN)
Interessen for adjuvant kjemoterapi hos pasienter med CINSARC Høyrisiko lokalisert reseksjonert uterin leiomyosarkom - Sarkom 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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Amel MEKALICHE, MS
- Telefonnummer: +33 761947045
- E-post: a-mekaliche@unicancer.fr
Studiesteder
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Angers, Frankrike, 49100
- Har ikke rekruttert ennå
- Institut de Cancerologie de L'Ouest (Ico)
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Hovedetterforsker:
- Patrick SOULIÉ, MD
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Besançon, Frankrike, 25030
- Har ikke rekruttert ennå
- Hopital Jean Minjoz
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Hovedetterforsker:
- Loic CHAIGNEAU, MD
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Bordeaux, Frankrike, 33076
- Har ikke rekruttert ennå
- Institut Bergonie
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Hovedetterforsker:
- Maud TOULMONDE, MD
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Caen, Frankrike, 14176
- Har ikke rekruttert ennå
- Centre Francois Baclesse
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Hovedetterforsker:
- Zoé NEVIERE, MD
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Clermont-Ferrand, Frankrike, 63011
- Har ikke rekruttert ennå
- Centre Jean Perrin
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Hovedetterforsker:
- Pascale DUBRAY-LONGERAS, MD
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Dijon, Frankrike, 21079
- Har ikke rekruttert ennå
- Centre Georges Francois Leclerc
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Hovedetterforsker:
- Isabelle DESMOULINS, MD
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Limoges, Frankrike, 87042
- Har ikke rekruttert ennå
- Chu Limoges
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Hovedetterforsker:
- Tiffany DARBAS, MD
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Lyon, Frankrike, 69373
- Har ikke rekruttert ennå
- Centre Léon Berard
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Hovedetterforsker:
- Isabelle RAY-COCUARD, MD PhD
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Marseille, Frankrike, 13273
- Har ikke rekruttert ennå
- Institut Paoli Calmettes
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Hovedetterforsker:
- François BERTUCCI, MD PhD
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Marseille, Frankrike, 13385
- Rekruttering
- La Timone University Hospital
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Hovedetterforsker:
- Florence DUFFAUD, MD PhD
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Nice, Frankrike, 06189
- Har ikke rekruttert ennå
- Centre Antoine Lacassagne
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Hovedetterforsker:
- Agnès DUCOULOMBIER, MD
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Paris, Frankrike, 75014
- Har ikke rekruttert ennå
- Hôpital Cochin
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Hovedetterforsker:
- Sixtine DE PERCIN, MD
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Paris, Frankrike
- Har ikke rekruttert ennå
- Institut Curie
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Hovedetterforsker:
- Clément BONET, MD
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Paris, Frankrike, 75010
- Har ikke rekruttert ennå
- Hopital Saint Louis
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Hovedetterforsker:
- Tiphaine LAMBERT, MD
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Paris, Frankrike, 75020
- Har ikke rekruttert ennå
- Groupe Hospitalier Diaconesses Croix St Simon
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Hovedetterforsker:
- Frédéric SELLE, MD
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Paris, Frankrike, 75020
- Har ikke rekruttert ennå
- Hopital Tenon
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Hovedetterforsker:
- Laurent SEKNAZI, MD
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Poitiers, Frankrike, 86000
- Har ikke rekruttert ennå
- Chu de Poitiers
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Hovedetterforsker:
- Nicolas ISAMBERT, MD PHD
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Rennes, Frankrike, 35042
- Har ikke rekruttert ennå
- Centre Eugene Marquis
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Hovedetterforsker:
- Christophe PERRIN, MD
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Rouen, Frankrike, 76038
- Har ikke rekruttert ennå
- Centre Henri Becquerel
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Hovedetterforsker:
- Cécile GUILLEMET, MD
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Saint-Herblain, Frankrike, 44805
- Har ikke rekruttert ennå
- Institut de cancerologie de l'ouest site Rene Gauducheau
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Hovedetterforsker:
- Pierre KUBICEK, MD
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Strasbourg, Frankrike
- Har ikke rekruttert ennå
- Institut de Cancerologie Strasbourg Europe (Icans)
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Ta kontakt med:
- Jean-Emmanuel KURTZ, MD
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Toulouse, Frankrike, 31052
- Har ikke rekruttert ennå
- Institut Claudius Regaud
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Hovedetterforsker:
- Thibaud VALENTIN, MD
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Tours, Frankrike, 37000
- Har ikke rekruttert ennå
- CHU Bretonneau
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Hovedetterforsker:
- Mathilde CANCEL, MD
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Vandœuvre-lès-Nancy, Frankrike, 54519
- Har ikke rekruttert ennå
- Centre Alexis Vautrin
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Hovedetterforsker:
- Maria RIOS, MD
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Villejuif, Frankrike, 94800
- Rekruttering
- Gustave Roussy
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Hovedetterforsker:
- Patricia PAUTIER, MD
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Ingen inngripen: Arm A
Standard of care : Active surveillance |
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Eksperimentell: 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)
Andre navn:
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Ingen inngripen: Prospective Cohort
Standard of care : Active surveillance |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Relapse-free survival
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Overall survival
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Florence DUFFAUD, MD, La TIMONE University Hospital
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Organiske kjemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ringen
- Hydrokarboner
- Hydrokarboner, syklisk
- Karbohydrater
- Polysykliske aromatiske hydrokarboner
- Hydrokarboner, aromatisk
- Polysykliske forbindelser
- Glykosider
- Antracykliner
- Naphthacenes
- Aminoglykosider
- Daunorubicin
- Dioksoler
- Tetrahydroisokinoliner
- Isokinoliner
- Trabectedin
- Doxorubicin
Andre studie-ID-numre
- UC-SAR-2212
- 2023-506350-21-00 (Ctis)
- 2023 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.
Legemiddel- og utstyrsinformasjon, studiedokumenter
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