Study of Doxorubicin and Trabectedin in First Line Treatment on Patients With Metastatic Leiomyosarcoma

Study Overview
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Brief Summary
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Uterine leiomyosarcomas and soft tissues are rare tumors with a poor prognosis when metastatic or locally advanced. They have an average chemosensitivity mainly to doxorubicin, ifosfamide, cisplatin, gemcitabine and trabectedin but response rates in combination in first line does not exceed 55% for uterine leiomyosarcomas and 35% for leiomyosarcomas of soft tissue. The trabectedin is a new cancer drug that has obtained marketing authorization after failure of anthracyclines and ifosfamide in the treatment of soft tissue sarcomas (STM) in Europe. It has especially shown efficacy in myxoid liposarcomas, leiomyosarcomas and synoviosarcoma. This study aims to evaluate the usefulness of the combination of trabectedin with doxorubicin in first-line treatment of uterine or soft tissue leiomyosarcoma.

Official Title
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A Multicentric Phase II Trial Studying Efficacy of Doxorubicin Associated With Trabectedin (Yondelis) in First Line Treatment on Patients With Metastatic Leiomyosarcoma (Uterus or Soft Tissue) and/or Inoperable Relapse

Conditions
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Uterus Leiomyosarcoma, Soft Tissue Leiomyosarcoma

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Trabectedin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic leiomyosarcoma (uterus or soft tissue) in inoperable relapse with no previous chemotherapy At least one measurable lesion according to RECIST criteria before inclusion. At least one of the target is in a none irradiated area Aged >/= 18 years and physiological age </= 70 years PS </= 2 Normal hematological function (Polymorphonuclear Neutrophils >/= 1500/mm3, platelets >/= 100 000/mm3) Normal kidney function (creatinine < 1.5xN) Creatinine phosphokinase </= 2.5xN Normal hepatic function (total bilirubin </= 1xN; transaminase </= 2.5xN and alkaline phosphatase </= 1.5xN) Cardiac function: normal echography and/or isotopic ventriculography (FR>30%, FEVG > 50%) Patients able to procreate must use a birth control device during treatment and during 3 months after treatment for women; 5 months for men Signed informed consent Patient under affiliated to a system of care Exclusion Criteria: Any other histological type of uterus sarcoma (carcinosarcoma...) or soft tissue Specific contraindication to the treatment Previous or evolutive mental disease Previous cancer Symptomatic or known brain metastasis Previous radiotherapy ont he only measurable lesion Previous allograft or autograft Known positive serology (HIV, HbC, HbS) Pregnant or breastfeeding women Impossibility to follow the treatment for geographical, social or mental reason Patients under legal protection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soft tissue<br> | Drug: Doxorubicin<br>* 60 mg/m²<br>* Other names: Adriamycin;Drug: Trabectedin<br>* 1,1 mg/m²<br>* Other names: Yondelis®;|
| Experimental: Uterus<br> | Drug: Doxorubicin<br>* 60 mg/m²<br>* Other names: Adriamycin;Drug: Trabectedin<br>* 1,1 mg/m²<br>* Other names: Yondelis®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | Disease control rate (objective response + stability) as defined by RECIST criteria | Assessed every 6 weeks from inclusion up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Assessed using RECIST criteria | Assessed every 6 weeks from inclusion up to 6 months | 
| Progression Free Survival |  | Assessed every 6 weeks from inclusion up to 12 weeks |