An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (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participants' consent is withdrawn or the eligibility criteria for continuing treatment are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