Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma
- Conditions
- Sarcoma
- Interventions
- Other: laboratory biomarker analysisProcedure: quality-of-life assessment
- Registration Number
- NCT01189253
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride and trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether trabectedin is more effective than doxorubicin hydrochloride in treating patients with advanced or metastatic soft tissue sarcoma.
PURPOSE: This randomized phase II/III trial is studying the safety of trabectedin compared with doxorubicin hydrochloride and to see how well they work in treating patients with advanced or metastatic soft tissue sarcoma.
- Detailed Description
OBJECTIVES:
* To evaluate whether trabectedin given as first-line chemotherapy for patients with previously untreated advanced or metastatic malignant soft tissue sarcoma prolongs progression-free survival as compared to doxorubicin hydrochloride.
* To identify and validate biomarkers (including, but not limited to, XPG, BRCA1, RAD51, BRCA2, ATM and CHK1) of sensitivity to trabectedin in order to allow the selection of patients that benefit most from trabectedin treatment. (Optional translational research)
OUTLINE: This is a multicenter, phase IIB study followed by a phase III study. Patients are stratified according to institution, age at registration (\< 60 years old vs ≥ 60 years old), and presence of liver metastases (yes vs no).
* Phase IIB (step 1): Patients are randomized to 1 of 3 treatment arms.
* Arm I: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive trabectedin IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive trabectedin IV continuously over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
At the end of step 1, the best regimen of trabectedin will be determined. Patients receiving the non-selected trabectedin regimen ("losing arm") are offered to cross over in order to receive the selected regimen of trabectedin.
* Phase III (step 2): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive trabectedin IV on day 1 using the preferred regimen determined in step 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life questionnaire (EORTC QLQ-C30 version 3) at baseline, at 6, 12, 24, and 36 weeks during study, and at the end of study.
Tumor tissue block obtained at diagnosis may be analyzed to identify and validate biomarkers of sensitivity to trabectedin and for tissue microarrays.
After completion of study therapy, patients are followed up at 1 month, every 6 or 12 weeks until disease progression, and every 12 weeks thereafter.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 133
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Doxorubicin 75 mg/m² every 3 weeks laboratory biomarker analysis Doxorubicin administered on day 1 every 3 weeks for a maximum of 6 cycles Doxorubicin 75 mg/m² every 3 weeks doxorubicin hydrochloride Doxorubicin administered on day 1 every 3 weeks for a maximum of 6 cycles Trabectedin IV 3 hours laboratory biomarker analysis Trabectedin administered on day 1 every 3 weeks at the dose of 1.3 mg/m² until progression Trabectedin IV 3 hours quality-of-life assessment Trabectedin administered on day 1 every 3 weeks at the dose of 1.3 mg/m² until progression Doxorubicin 75 mg/m² every 3 weeks quality-of-life assessment Doxorubicin administered on day 1 every 3 weeks for a maximum of 6 cycles Trabectedin IV 24 hours every 3 weeks laboratory biomarker analysis Trabectedin administered on day 1 every 3 weeks at the dose of 1.5 mg/m² over 24 hours until progression Trabectedin IV 24 hours every 3 weeks quality-of-life assessment Trabectedin administered on day 1 every 3 weeks at the dose of 1.5 mg/m² over 24 hours until progression Trabectedin IV 3 hours trabectedin Trabectedin administered on day 1 every 3 weeks at the dose of 1.3 mg/m² until progression Trabectedin IV 24 hours every 3 weeks trabectedin Trabectedin administered on day 1 every 3 weeks at the dose of 1.5 mg/m² over 24 hours until progression
- Primary Outcome Measures
Name Time Method Progression-free survival as assessed by RECIST v 1.1 criteria (phase IIB and phase III) Safety (phase IIB)
- Secondary Outcome Measures
Name Time Method Overall survival (phase III) Response rate and response duration (phase III) Safety profile (phase III) Quality of life (phase III)
Trial Locations
- Locations (43)
ASSISTANCE PUBLIQUE - HôPITAUX DE MARSEILLE - HôPITAL DE LA TIMONE
🇫🇷Marseille, France
Methodist Estabrook Cancer Center
🇺🇸Omaha, Nebraska, United States
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Klinikum Grosshadern Ludwig-Maximilians Univ. Muenchen
🇩🇪Muenchen, Germany
Leiden University Medical Centre
🇳🇱Leiden, Netherlands
Centre Leon Berard
🇫🇷Lyon, France
Universitaetsmedizin Mannheim
🇩🇪Mannheim, Germany
Military Hospital - State Health Centre
🇭🇺Budapest, Hungary
National Cancer Institute
🇸🇰Bratislava, Slovakia
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Netherlands
Erasmus Mc - Daniel Den Hoed Cancer Center
🇳🇱Rotterdam, Netherlands
Massachussets General Hospital
🇺🇸Boston, Massachusetts, United States
Pennsylvania Oncology Hematology Associates, Incorporated - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
HôPITAUX UNIVERSITAIRES BORDET-ERASME - INSTITUT JULES BORDET
🇧🇪Brussels, Belgium
Institut Bergonie
🇫🇷Bordeaux, France
Centre Oscar Lambret
🇫🇷Lille, France
Institut de Cancerologie de L'Ouest (Ico) - Centre Rene Gauducheau
🇫🇷Nantes - St. Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Nhs Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Christie Nhs Foundation Trust
🇬🇧Manchester, United Kingdom
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Nottingham University Hospitals Nhs Trust - City Hospital Campus
🇬🇧Nottingham, United Kingdom
Dana Farber Institute
🇺🇸Boston, Massachusetts, United States
Centre Georges-Francois-Leclerc
🇫🇷Dijon, France
Herlev Hospital - University Copenhagen
🇩🇰Herlev, Denmark
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Medical University Vienna
🇦🇹Vienna, Austria
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Cliniques Universitaires St. Luc
🇧🇪Brussels, Belgium
Carolinas Hematology-Oncology Associates
🇺🇸Charlotte, North Carolina, United States
Hospital General Vall D'Hebron
🇪🇸Barcelona, Spain
Institut Curie
🇫🇷Paris, France
Universitaets-Krankenhaus Eppendorf
🇩🇪Hamburg, Germany
Helios Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Universitaetsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Maria Sklodowska-Curie Memorial Cancer Centre
🇵🇱Warsaw, Poland
Hospital Universitario San Carlos
🇪🇸Madrid, Spain