NCT01189253

Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma

TRUSTS: A Phase IIB/III Multicenter Study Comparing the Efficacy of TRabectedin Administered as a 3-Hour or 24-Hour Infusion to Doxorubicin in Patients With Advanced or Metastatic Untreated Soft Tissue Sarcoma

• Status: Terminated
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 133 (actual)
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Sarcoma

Interventions

Type	Name	Description
DRUG	doxorubicin hydrochloride
DRUG	trabectedin
OTHER	laboratory biomarker analysis
PROCEDURE	quality-of-life assessment

Timeline

• Start date: 2011-05-01
• Primary completion: 2013-06-01
• Completion: 2015-06-01
• First posted: 2010-08-26
• Last updated: 2014-08-08

Locations

43 sites across 13 countries: United States, Austria, Belgium, Denmark, France, Germany, Hungary, Netherlands, Poland, Slovakia, Spain, Switzerland, United Kingdom