Uterine or Soft Tissue LeiomyosarcomaPhase 3LMS04NCT02997358
Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin Versus Doxorubicine in Patients With Leiomyosarcoma
A Phase 3 study testing Doxorubicin and Trabectedin in people with Uterine or Soft Tissue Leiomyosarcoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uterine or Soft Tissue Leiomyosarcoma
- What is being tested?
- Doxorubicin and Trabectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteFrance
- Study dates
- 18 Jan 2017to 28 Jul 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read more
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
- Being tested
- Doxorubicin, Trabectedin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
75 mg/m² Day 1 of each 3-weeks cycle
TrabectedinDrug
150 μg/m²/day s.c From day 3 to day 9
| Study group | Role | What they receive |
|---|---|---|
| Doxorubicin | Active comparator | 6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV Receives: 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 Receives: Drug: Doxorubicin; Drug: Trabectedin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free Survival
Tumour assessment will be analysed using RECIST 1.1 criteria.
Measured: Until progression or 2 years after randomization, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study start18 Jan 2017
- Primary completion28 Jul 2021
- Study completion28 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Uterine or Soft Tissue LeiomyosarcomaStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997358
- Sponsor's protocol ID
- 2016-002186-56
- Other IDs
- 2016/2410, 2016
- Acronym
- LMS04
- Status last verified
- Dec 2021
- First submitted
- 13 Dec 2016
- Last updated
- 30 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39231341Pautier 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.
PubMed 35835135Hanvic 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.
PubMed 34009140
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02997358
- Acronym / sponsor ID
- LMS04 / 2016-002186-56
- Conditions
- Uterine or Soft Tissue Leiomyosarcoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- 18 Jan 2017 (actual)
- Primary completion
- 28 Jul 2021 (actual)
- Study completion
- 28 Jul 2021 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxorubicin | Active comparator | Drug: Doxorubicin6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV |
| doxorubicin + trabectedin followed by maintenance trabectedin | Experimental | Drug: Doxorubicin, Drug: Trabectedin1. 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxorubicin75 mg/m² Day 1 of each 3-weeks cycle | Drug | Doxorubicin, doxorubicin + trabectedin followed by maintenance trabectedin |
| Trabectedin150 μg/m²/day s.c From day 3 to day 9 | Drug | doxorubicin + trabectedin followed by maintenance trabectedin |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2021.
- Derived from this study: PubMed 39231341Pautier 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.
- Derived from this study: PubMed 35835135Pautier 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.
- Derived from this study: PubMed 34009140Hanvic 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.
- Individual participant dataSharing planned: No
Related trials for Uterine or Soft Tissue Leiomyosarcoma
Active, not recruitingPhase 2
Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma
Metastatic Leiomyosarcoma, Metastatic Soft Tissue Sarcoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 2
Pazopanib Vs. Pazopanib Plus Gemcitabine
Leiomyosarcoma or Carcinosarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxorubicin and Trabectedin in people with Uterine or Soft Tissue Leiomyosarcoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free Survival (time frame: Until progression or 2 years after randomization, whichever occurs first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02997358, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2021.