Trial Title:
Interest of Post-operative Chemotherapy in Patients With Localised Uterine Leiomyosarcoma Suspected of Having a High Risk of Recurrence Based on a Biological Test Performed on the Tumour
NCT ID:
NCT06524583
Condition:
Leiomyosarcoma Uterus
Conditions: Official terms:
Leiomyosarcoma
Doxorubicin
Trabectedin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Multicenter, randomized and comparative phase II trial and prospective cohort
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
60 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
Arm group label:
Arm B
Intervention type:
Drug
Intervention name:
Trabectedin
Description:
1.1 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
Arm group label:
Arm B
Other name:
Yondelis
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
Criteria for eligibility:
Criteria:
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:
- Exclusion criteria:
1. All other histology types of uterine sarcoma (adenosarcoma, endometrial
sarcoma, undifferentiated uterine sarcoma)
2. 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
3. Planned pelvic post-operative radiation therapy
4. Metastatic or measurable disease on CT-Scan
5. Known hypersensitivity to doxorubicin or trabectedin or to any of the
excipients
6. Any contra-indication for the use of doxorubicin and/or trabectedin treatment
7. Participation in another therapeutic trial within the 30 days prior to
inclusion in the study
8. Active viral hepatitis B or C or known human immunodeficiency virus (HIV)
infection.
9. 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)
10. 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) 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 :
1. Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a sarcoma
expert pathologist or by the study central pathologist
2. Patients with a low-risk CINSARC signature
Gender:
Female
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut de Cancerologie de L'Ouest (Ico)
Address:
City:
Angers
Zip:
49100
Country:
France
Investigator:
Last name:
Patrick SOULIÉ, MD
Email:
Principal Investigator
Facility:
Name:
Hopital Jean Minjoz
Address:
City:
Besancon
Zip:
25030
Country:
France
Investigator:
Last name:
Loic CHAIGNEAU, MD
Email:
Principal Investigator
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Investigator:
Last name:
Maud TOULMONDE, MD
Email:
Principal Investigator
Facility:
Name:
Centre Francois Baclesse
Address:
City:
Caen
Zip:
14176
Country:
France
Investigator:
Last name:
Zoé NEVIERE, MD
Email:
Principal Investigator
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Investigator:
Last name:
Pascale DUBRAY-LONGERAS, MD
Email:
Principal Investigator
Facility:
Name:
Centre Georges Francois Leclerc
Address:
City:
Dijon
Zip:
21079
Country:
France
Investigator:
Last name:
Isabelle DESMOULINS, MD
Email:
Principal Investigator
Facility:
Name:
Chu Limoges
Address:
City:
Limoges
Zip:
87042
Country:
France
Investigator:
Last name:
Tiffany DARBAS, MD
Email:
Principal Investigator
Facility:
Name:
Centre Léon Berard
Address:
City:
Lyon
Zip:
69373
Country:
France
Investigator:
Last name:
Isabelle RAY-COCUARD, MD PhD
Email:
Principal Investigator
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13273
Country:
France
Investigator:
Last name:
François BERTUCCI, MD PhD
Email:
Principal Investigator
Facility:
Name:
La Timone University Hospital
Address:
City:
Marseille
Zip:
13385
Country:
France
Investigator:
Last name:
Florence DUFFAUD, MD PhD
Email:
Principal Investigator
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Zip:
06189
Country:
France
Investigator:
Last name:
Agnès DUCOULOMBIER, MD
Email:
Principal Investigator
Facility:
Name:
Hopital Saint Louis
Address:
City:
Paris
Zip:
75010
Country:
France
Investigator:
Last name:
Tiphaine LAMBERT, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Cochin
Address:
City:
Paris
Zip:
75014
Country:
France
Investigator:
Last name:
Sixtine DE PERCIN, MD
Email:
Principal Investigator
Facility:
Name:
Groupe Hospitalier Diaconesses Croix St Simon
Address:
City:
Paris
Zip:
75020
Country:
France
Investigator:
Last name:
Frédéric SELLE, MD
Email:
Principal Investigator
Facility:
Name:
Hopital Tenon
Address:
City:
Paris
Zip:
75020
Country:
France
Investigator:
Last name:
Laurent SEKNAZI, MD
Email:
Principal Investigator
Facility:
Name:
Institut Curie
Address:
City:
Paris
Country:
France
Investigator:
Last name:
Clément BONET, MD
Email:
Principal Investigator
Facility:
Name:
Chu de Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Investigator:
Last name:
Nicolas ISAMBERT, MD PHD
Email:
Principal Investigator
Facility:
Name:
Centre Eugene Marquis
Address:
City:
Rennes
Zip:
35042
Country:
France
Investigator:
Last name:
Christophe PERRIN, MD
Email:
Principal Investigator
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Zip:
76038
Country:
France
Investigator:
Last name:
Cécile GUILLEMET, MD
Email:
Principal Investigator
Facility:
Name:
Institut de cancerologie de l'ouest site Rene Gauducheau
Address:
City:
Saint Herblain
Zip:
44805
Country:
France
Investigator:
Last name:
Pierre KUBICEK, MD
Email:
Principal Investigator
Facility:
Name:
Institut de Cancerologie Strasbourg Europe (Icans)
Address:
City:
Strasbourg
Country:
France
Contact:
Last name:
Jean-Emmanuel KURTZ, MD
Facility:
Name:
Institut Claudius Regaud
Address:
City:
Toulouse
Zip:
31052
Country:
France
Investigator:
Last name:
Thibaud VALENTIN, MD
Email:
Principal Investigator
Facility:
Name:
CHU Bretonneau
Address:
City:
Tours
Zip:
37000
Country:
France
Investigator:
Last name:
Mathilde CANCEL, MD
Email:
Principal Investigator
Facility:
Name:
Centre Alexis Vautrin
Address:
City:
Vandoeuvre-les-nancy
Zip:
54519
Country:
France
Investigator:
Last name:
Maria RIOS, MD
Email:
Principal Investigator
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94800
Country:
France
Investigator:
Last name:
Patricia PAUTIER, MD
Email:
Principal Investigator
Start date:
October 2024
Completion date:
December 2030
Lead sponsor:
Agency:
UNICANCER
Agency class:
Other
Collaborator:
Agency:
PharmaMar
Agency class:
Industry
Collaborator:
Agency:
Ligue contre le cancer, France
Agency class:
Other
Collaborator:
Agency:
National Research Agency, France
Agency class:
Other
Collaborator:
Agency:
University Hospital, Marseille
Agency class:
Other
Collaborator:
Agency:
Institut Claudius Regaud
Agency class:
Other
Collaborator:
Agency:
Institut Bergonié
Agency class:
Other
Collaborator:
Agency:
Oncopole
Agency class:
Other
Source:
UNICANCER
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06524583
