Informations générales (source: ClinicalTrials.gov)
Randomized, Controlled, Open-label, Phase III Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Patients With Metastatic Leiomyosarcoma
Interventional
Phase 3
PharmaMar (Voir sur ClinicalTrials)
septembre 2023
août 2029
02 octobre 2025
The primary objective of this phase III study is to evaluate whether the combination of
lurbinectedin plus doxorubicin given as first line treatment for metastatic
leiomyosarcoma (LMS) prolongs the progression-free survival (PFS) by Independent Review
Committee (IRC) when compared to doxorubicin administered as a single agent.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:07 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Axel LE CESNE | 17/05/2024 12:08:55 | Contacter | ||
Critères
Tous
1. Voluntary signed and dated written informed consent of the participants obtained
before any study-specific procedure.
2. Age ≥ 18 years.
3. Histologically confirmed diagnosis of metastatic LMS, in participants not candidates
for curative resection.
4. Radiologically measurable disease according to the Response Evaluation Criteria in
Solid Tumors (RECIST) v.1.1.
5. No previous systemic therapy for metastatic disease (i.e., first-line setting) and
no previous anthracyclines. Note: prior chemotherapy (without anthracycline) in the
context of adjuvant or neoadjuvant therapy is allowed. Prior line/s of hormone
therapy in the adjuvant/metastatic setting are also allowed.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
7. Adequate hematological, renal, metabolic and hepatic function:
1. Hemoglobin ≥ 9.0 g/dL (participants may have received prior red blood cell [Red
Blood Cell] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and
platelet count
≥ 100 x 10^9/L.
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x
upper limit of normal (ULN).
3. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is >
ULN.
4. Albumin ≥ 3.0 g/dL.
5. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's
formula).
6. Left ventricular ejection fraction (LVEF) > 50% assessed by multiple-gated
acquisition scan (MUGA) or echocardiography (ECHO) or cardiac magnetic
resonance imaging (MRI).
8. Wash-out periods:
1. At least three weeks since last prior systemic treatment.
2. At least three weeks since last prior major surgery and one week since last
prior minor surgery (port placement is excluded from this wash-out period).
3. At least two weeks since last prior radiotherapy.
9. Evidence of non-childbearing status for women of childbearing potential (WOCBP).
WOCBP must agree to use a highly effective contraceptive measure up to seven months
after treatment discontinuation. Fertile male participants with WOCBP partners
should use condoms during treatment and for four months following the last
investigational medicinal product (IMP) dose.
Exclusion Criteria:
1. Prior treatment with anthracyclines, lurbinectedin or trabectedin.
2. Known low grade leiomyosarcoma (i.e., grade I).
3. Known hypersensitivity to any of the components of the IV formulation of
lurbinectedin or doxorubicin.
4. Concomitant diseases/conditions:
1. History of cardiac disease: myocardial infarction or angina within the year
prior to enrollment; severe vascular disease; or symptomatic arrhythmia despite
ongoing treatment.
2. Participants with any immunodeficiency, including those known to be infected by
human immunodeficiency virus (HIV).
3. Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includes
positive tests for both Hepatitis B surface antigen and quantitative Hepatitis
B polymerase chain reaction (PCR). For Hepatitis C, this includes positive
tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
4. Active uncontrolled infection.
5. Any other major illness that (including severe cardiovascular disease) or risk
factors that, in the Investigator's judgment, will substantially increase the
risk associated with the patient's participation in this study.
5. Use of strong inducers of CYP3A4 activity within two weeks prior to the first
infusion of lurbinectedin.
6. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is
available, unless progression of the lesion has been confirmed.
7. Known myopathy (history of resolved steroid-induced myopathy is allowed).
8. History of malignancies other than LMS within three years prior to enrollment,
except for malignancies with a negligible risk of metastasis or death (e.g., 5-year
OS rate >90%), such as adequately treated carcinoma in situ of the cervix,
non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive
urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior
malignancies should have received curative treatment and should remain in remission.
The Investigator should ensure, based on histology or clinical information, that the
current metastatic sites are leiomyosarcoma and not recurrence of the original
malignancy.
9. Limitation of the participant's ability to comply with the treatment or to follow-up
the protocol.
10. Women who are pregnant or breast feeding and fertile participants (men and women)
who are not using a highly effective method of contraception.
11. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to
a critical structure).