A Study of the Safety and Effectiveness of Trabetedin Versus Doxorubicin-based Chemotherapy in Patients With Translocation-Related Sarcomas (TRS)

• Progression - Free Survival [ Time Frame: Up to approximately 20 months ] [ Designated as safety issue: No ]
• Best objective response [ Time Frame: Up to approximately 20 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: Up to approximately 20 months ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: Up to approximately 20 months ] [ Designated as safety issue: No ]
• Incidence of adverse events [ Time Frame: Up to approximately 20 months ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate the effectiveness of trabetedin compared to standard doxorubicin-based chemotherapy as first-line treatment in patients with advanced Translocation-Related Sarcomas (a type of cancer).

This is a randomized (patients will be assigned to treatment by chance), multicenter, Phase III trial to evaluate the effectiveness of trabectedin versus standard doxorubicin-based chemotherapy (DXCT) as first-line treatment of patients with advanced Translocation-Related Sarcomas (TRS) (a type of cancer), by comparing progression-free survival (PFS) in the two treatment arms (Treatment Arm A: Trabectedin; Treatment Arm B: Doxorubicin as a single agent or in combination with ifosfamide). Trabectedin 1.5 mg/m2 given intravenously (i.v.) over 24-hours; or doxorubicin 75 mg/m2 i.v. every 3 weeks, or doxorubicin 60 mg/m2 i.v.followed by ifosfamide in the range of 6 to 9 g/m2 every 3 weeks with proper hydration and ifosfamide chemoprotectant drugs.

• Translocation, Genetic
• Sarcoma, Soft Tissue

• Drug: Trabectedin
  1.5 mg/m2 administered as a 24-hour i.v. infusion every three weeks
• Drug: Doxorubicin
  75 mg/m2 i.v. every three weeks

• Experimental: 001
  Trabectedin 1.5 mg/m2 administered as a 24-hour i.v. infusion every three weeks
  Intervention: Drug: Trabectedin
• Active Comparator: 002
  Doxorubicin 75 mg/m2 i.v. every three weeks or 60 mg/m2 i.v. followed by ifosfamide range 6 to 9 g/m2 i.v.every three weeks
  Intervention: Drug: Doxorubicin

Inclusion Criteria:

• Pathological diagnosis of TRS (institutional assessment)
• Patients must have unresectable locally advanced or metastatic disease prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2
• Adequate cardiac function.

Exclusion Criteria:

• Known hypersensitivity to any components of the i.v. formulation of trabectedin or the comparator
• Prior chemotherapy treatment of irradiation of the lesion
• Brain metastases and/or leptomeningeal metastases, even if treated
• Pregnant or lactating women
• History of another neoplastic disease unless in remission for five years or more. Other serious illnesses such as congestive heart failure or angina pectoris, myocardial infarction within 1 year before enrollment, uncontrolled arterial hypertension or arrhythmias.