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

NCT ID: NCT02997358

Last Updated: 2021-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-18

Study Completion Date

2021-07-28

Brief Summary

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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.

Detailed Description

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Conditions

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Uterine or Soft Tissue Leiomyosarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Doxorubicin

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

Group Type ACTIVE_COMPARATOR

Doxorubicin

Intervention Type DRUG

75 mg/m² Day 1 of each 3-weeks cycle

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

Group Type EXPERIMENTAL

Doxorubicin

Intervention Type DRUG

75 mg/m² Day 1 of each 3-weeks cycle

Trabectedin

Intervention Type DRUG

150 μg/m²/day s.c From day 3 to day 9

Interventions

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Doxorubicin

75 mg/m² Day 1 of each 3-weeks cycle

Intervention Type DRUG

Trabectedin

150 μg/m²/day s.c From day 3 to day 9

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Gustave Roussy

Villejuif, Val De Marne, France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 39231341 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35835135 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34009140 (View on PubMed)

Other Identifiers

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2016/2410

Identifier Type: OTHER

Identifier Source: secondary_id

2016-002186-56

Identifier Type: -

Identifier Source: org_study_id