An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)

A Randomized, Multicenter, Phase III Trial of Trabectedin (Yondelis) Versus Doxorubicin-based Chemotherapy as First-Line Therapy in Patients With Translocation-Related Sarcomas (TRS)

The purpose of this study is to evaluate the efficacy and safety of trabectedin compared to standard doxorubicin in participants with advanced translocation-related sarcomas (cancer of connective tissue cells) (TRS).

This is a randomized (study drug assigned by chance), multicenter (when more than one hospital or medical school team work on a medical research study), Phase 3 trial to evaluate the efficacy and safety of trabectedin as compared to standard doxorubicin in participants with advanced TRS. Participants will be randomized in a 1:1 ratio to either of the 2 treatment groups, that is, trabectedin or doxorubicin plus ifosfamide group. Participants in trabectedin group will receive trabectedin 1.5 milligram per square meter (mg/m^2) given as a 24-hour continuous intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) every 3 weeks and in doxorubicin plus ifosfamide group participants will receive doxorubicin 60 or 75 mg/m^2 intravenously every 3 weeks followed by ifosfamide 6 to 9 gram (g)/m^2 every 3 weeks. Participants in either treatment arm will continue receiving therapy in the absence of progressive disease (PD) or intolerable side effects, until the participants' consent is withdrawn or the eligibility criteria for continuing treatment are no longer fulfilled, or when a concurrent condition precludes continuation of treatment. Efficacy will be assessed primarily by evaluating progression-free survival (PFS). Participants' safety will be monitored throughout the trial.

Inclusion Criteria:

• Pathological diagnosis of translocation-related sarcomas (TRS) including the following subtypes: alveolar soft part sarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, low grade endometrial stromal sarcoma (prior hormone therapy allowed), low grade fibromyxoid sarcoma, myxoid chondrosarcoma, myxoid/round cell liposarcoma (MRCL) and synovial sarcoma
• Participants must have unresectable locally advanced or metastatic progressive disease prior to enrolment
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2
• Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) within normal limits according to institutional standards, as shown by echocardiography or scintigraphy multiple-gated acquisition scan [MUGA]
• Measurable disease as defined by the radiological (computed tomography [CT] scan and magnetic resonance imaging [MRI]) Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) guidelines

Exclusion Criteria:

• Known hypersensitivity to any components of the intravenous formulation of trabectedin or the comparators
• Prior chemotherapy treatment or irradiation of the lesion if only one target lesion is available
• Brain metastases and/or leptomeningeal metastases, even if treated
• Pregnant or lactating women or men and women of reproductive potential who are not using effective contraceptive methods
• History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for five years or more