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Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin Versus Doxorubicine in Patients With Leiomyosarcoma (LMS04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02997358
Recruitment Status : Completed
First Posted : December 20, 2016
Last Update Posted : December 30, 2021
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Uterine or Soft Tissue Leiomyosarcoma Drug: Doxorubicin Drug: Trabectedin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : January 18, 2017
Actual Primary Completion Date : July 28, 2021
Actual Study Completion Date : July 28, 2021

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
Drug: Doxorubicin
75 mg/m² Day 1 of each 3-weeks cycle

Experimental: doxorubicin + trabectedin followed by maintenance trabectedin
  1. Doxorubicin + trabectedin 6 cycles - 1 cycle every 3 weeks (day 1 to day 21) Doxorubicin 60 mg/m² IV D1, then Trabectedin 1.1 mg/m² per CIV 3 hours D1. Surgery for residual disease is possible after 6 cycles (in case of non evolutive disease)
  2. In case of response or stable disease after 6 cycles 3-weeks cycle until disease progression or for a maximum of 12 months of treatment (maximum 17 cycles in maintenance therapy), whichever occurs first Trabectedin 1.1 mg/m² per CIV 3 hours
Drug: Doxorubicin
75 mg/m² Day 1 of each 3-weeks cycle

Drug: Trabectedin
150 μg/m²/day s.c From day 3 to day 9

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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
  2. 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.
  3. Age ≥ 18 years old
  4. ECOG performance status < 2 (Appendix 4)
  5. 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%
  6. Creatinin phosphokinase (CPK) ≤ 2.5 x ULN
  7. 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.
  8. Signed written informed consent form
  9. Patient affiliated to a social security regimen or beneficiary of the same

Exclusion Criteria:

  1. All other histological types of uterine sarcomas or soft tissue sarcomas
  2. Any contraindication for the use of trabectedin and/or doxorubicin (cardiac, renal, hepatic, known hypersensitivity…)
  3. Patient already enrolled in another therapeutic trial involving an investigational substance, and when such a substance has been taken during the previous 4 weeks.
  4. Medical history of progressive psychiatric disorder
  5. 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.
  6. Known cerebral metastasis
  7. History of allograft or autograft
  8. Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection
  9. Pregnant women or nursing mothers
  10. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02997358

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Gustave Roussy
Villejuif, Val De Marne, France, 94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris Identifier: NCT02997358    
Other Study ID Numbers: 2016-002186-56
2016/2410 ( Other Identifier: CSET number )
First Posted: December 20, 2016    Key Record Dates
Last Update Posted: December 30, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents