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

NCT02997358 | Completed Phase 3

• 2 other identifiers: 2016-002186-562016/2410
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Uterine or Soft Tissue Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Progression free Survival

  Tumour assessment will be analysed using RECIST 1.1 criteria.

  Until progression or 2 years after randomization, whichever occurs first

Study Arms (2)

Doxorubicin

ACTIVE COMPARATOR

6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV

Drug: Doxorubicin

doxorubicin + trabectedin followed by maintenance trabectedin

EXPERIMENTAL

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; Drug: Trabectedin

Interventions

Doxorubicin DRUG

75 mg/m² Day 1 of each 3-weeks cycle

Doxorubicin; doxorubicin + trabectedin followed by maintenance trabectedin

Trabectedin DRUG

150 μg/m²/day s.c From day 3 to day 9

doxorubicin + trabectedin followed by maintenance trabectedin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Signed written informed consent form
• Patient affiliated to a social security regimen or beneficiary of the same

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Related Publications (3)

• Pautier P, Italiano A, Piperno-Neumann S, Chevreau C, Penel N, Firmin N, Boudou-Rouquette P, Bertucci F, Lebrun-Ly V, Ray-Coquard I, Kalbacher E, Bompas E, Collard O, Isambert N, Guillemet C, Rios M, Le Cesne A, Balleyguier C, Archambaud B, Duffaud F; French Sarcoma Group. Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma. N Engl J Med. 2024 Sep 5;391(9):789-799. doi: 10.1056/NEJMoa2403394.

  PMID: 39231341 DERIVED

• 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.

  PMID: 35835135 DERIVED

• 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.

  PMID: 34009140 DERIVED

MeSH Terms

Interventions

Doxorubicin; Trabectedin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: December 20, 2016
• Study Start: January 18, 2017
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: December 30, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)