- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02997358
Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin Versus Doxorubicine in Patients With Leiomyosarcoma (LMS04)
Randomised Phase III Multicentric Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin in Non-progressive Patients Versus Doxorubicine Alone as First-line Therapy in Patients With Metastatic or Unresectable Leiomyosarcoma (Uterine or Soft Tissue)
The objective of LMS04 study is to better define the treatment strategy for patients with metastatic leiomyosarcoma (uterine or soft tissue), as well as identifying the best first line therapeutic option for these patients. LMS04 will test a new strategy for first line therapy LMS sarcoma compare to the reference therapy (6 cycles of doxorubicin alone): the interest of the association of trabectedin to doxorubicin in first line treatment followed by trabectedin alone for non-progressive patients after 6 cycles of the association of trabectedin and doxorubicin (the LMS02 design).
LMS04 will be the first phase III randomized study specifically dedicated to soft tissue leiomyosarcoma in first line metastatic disease.
It is planned to compare a new doxorubicin combination (including trabectedin) with very encouraging results followed by trabectedin maintenance therapy for non-progressive patients to doxorubicin alone. Prospective ancillary translational studies will attempt to define profiles of patients who could benefit from this new chemotherapy in an exploratory way.
The validation of a new first line option specific for LMS, identifying clinical factors that characterize aggressiveness and responsiveness to treatment aims to have an important in the spirit of personalized medicine in this rare and deadly disease.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Val De Marne
-
Villejuif, Val De Marne, France, 94805
- Gustave Roussy
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have histologically confirmed diagnosis of metastatic or relapsed unresectable uterine or soft tissue leiomyosarcoma, reviewed in a reference center (among RREPS network), previously untreated with chemotherapy , and with available Formalin Fixed Paraffin Embedded (FFPE) blocks
- At least one measurable lesion according to RECIST V 1.1 criteria. Target could be in a previously irradiated field but has to be progressive or a biopsy had to be positive before inclusion.
- Age ≥ 18 years old
- ECOG performance status < 2 (Appendix 4)
Adequate haematological, liver and cardiac functions:
- Neutrophil counts ≥ 1500/mm3
- Platelets ≥ 100 000/mm3
- Serum creatinin < 1.5 x Upper Limit of Normal Value (UNL)
- Serum bilirubin ≤1 x ULN
- ALT, AST ≤ 2.5 x ULN
- Alcaline phosphatases ≤ 1.5 x ULN
- Cardiac ultrasound and/or normal isotopic ventriculography : Shortening Fraction (SF) > 30%, Left Ventricular Ejection Fraction (LVEF) > 50%
- Creatinin phosphokinase (CPK) ≤ 2.5 x ULN
- Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to inclusion. Both males and WOCBP who are sexually active should be using an effective birth control method from inclusion (for WOCBP) or treatment initiation (for male) and up to 6 months following the last dose of study drug.
- Signed written informed consent form
- Patient affiliated to a social security regimen or beneficiary of the same
Exclusion Criteria:
- All other histological types of uterine sarcomas or soft tissue sarcomas
- Any contraindication for the use of trabectedin and/or doxorubicin (cardiac, renal, hepatic, known hypersensitivity…)
- Patient already enrolled in another therapeutic trial involving an investigational substance, and when such a substance has been taken during the previous 4 weeks.
- Medical history of progressive psychiatric disorder
- History of another type of cancer not in complete remission for more than 3 years prior to study entry (except for cutaneous basal cell carcinoma or in situ cervical epithelioma), and/or having required any chemotherapy treatment at any time.
- Known cerebral metastasis
- History of allograft or autograft
- Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection
- Pregnant women or nursing mothers
- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or any condition (e.g., psychological instability, geographical location, social reason, etc.) that, in the judgment of the Investigator, may affect the patient's ability to understand and sign the informed consent or to fully comply with all study visits, treatments, procedures, and other requirements scheduled in the protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Doxorubicin
6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV
|
75 mg/m² Day 1 of each 3-weeks cycle
|
EXPERIMENTAL: doxorubicin + trabectedin followed by maintenance trabectedin
|
75 mg/m² Day 1 of each 3-weeks cycle
150 μg/m²/day s.c From day 3 to day 9
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free Survival
Time Frame: Until progression or 2 years after randomization, whichever occurs first
|
Tumour assessment will be analysed using RECIST 1.1 criteria.
|
Until progression or 2 years after randomization, whichever occurs first
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Pautier P, Italiano A, Piperno-Neumann S, Chevreau C, Penel N, Firmin N, Boudou-Rouquette P, Bertucci F, Balleyguier C, Lebrun-Ly V, Ray-Coquard I, Kalbacher E, Bardet A, Bompas E, Collard O, Isambert N, Guillemet C, Rios M, Archambaud B, Duffaud F; French Sarcoma Group. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2022 Aug;23(8):1044-1054. doi: 10.1016/S1470-2045(22)00380-1. Epub 2022 Jul 11.
- Hanvic B, Ray-Coquard I. Gynecological sarcomas: literature review of 2020. Curr Opin Oncol. 2021 Jul 1;33(4):345-350. doi: 10.1097/CCO.0000000000000753.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Neoplasms, Muscle Tissue
- Leiomyosarcoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Doxorubicin
- Trabectedin
Other Study ID Numbers
- 2016-002186-56
- 2016/2410 (OTHER: CSET number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uterine or Soft Tissue Leiomyosarcoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Leiomyosarcoma | Stage III Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 | Unresectable Leiomyosarcoma | Stage IIIA Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IIIB Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IIIC Uterine Corpus Leiomyosarcoma... and other conditionsUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)RecruitingLocally Advanced Leiomyosarcoma | Metastatic Leiomyosarcoma | Stage III Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 | Unresectable Leiomyosarcoma | Uterine Corpus LeiomyosarcomaUnited States
-
National Cancer Institute (NCI)RecruitingLocally Advanced Uterine Corpus Leiomyosarcoma | Metastatic Uterine Corpus Leiomyosarcoma | Stage III Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 | Unresectable Uterine Corpus LeiomyosarcomaUnited States, Puerto Rico
-
National Cancer Institute (NCI)Active, not recruitingStage III Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 | Uterine Corpus LeiomyosarcomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Leiomyosarcoma | Unresectable Leiomyosarcoma | Uterine Corpus LeiomyosarcomaUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)TerminatedUterine Corpus Leiomyosarcoma | Stage I Uterine Sarcoma AJCC v7United States, Belgium, France, Spain, United Kingdom, Netherlands, Norway, Venezuela
-
West China Second University HospitalActive, not recruitingUterine Sarcoma | Uterine Fibroid | Uterine LeiomyosarcomaChina
-
Kristen GanjooRecruitingUterine Leiomyosarcoma | LMS - LeiomyosarcomaUnited States
-
Gynecologic Oncology GroupGlaxoSmithKlineWithdrawnUterine Leiomyosarcoma
Clinical Trials on Doxorubicin
-
Azaya Therapeutics, Inc.UnknownCancer | Ovarian Cancer | Ovarian Epithelial Cancer Recurrent | Malignant Female Reproductive System Neoplasm | Ovarian TumorCanada, United States
-
National Cancer Institute (NCI)CompletedDS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | Male Breast Carcinoma | Stage IV Breast Cancer AJCC...United States
-
OnxeoCompletedCarcinoma, HepatocellularItaly, Spain, United States, Belgium, Austria, France, Egypt, Germany, Hungary, Turkey, Lebanon
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Completed
-
Sohag UniversityActive, not recruiting
-
AEterna ZentarisCompletedEndometrial CancerUnited States, Spain, Canada, Ireland, Norway, Austria, Denmark, Israel, United Kingdom, Belgium, Finland, Romania, Czechia, Italy, Poland, Germany, Netherlands, Belarus, Bosnia and Herzegovina, Bulgaria, Russian Federation, Ukraine
-
SOLTI Breast Cancer Research GroupCompleted
-
Falo, Louis, MDActive, not recruitingCutaneous T Cell LymphomaUnited States
-
Boston Scientific CorporationBiocompatibles UK LtdCompletedPrimary Liver CancerAustria, Switzerland, France, Germany