A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma

• Progression-free survival [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
• Time to progression [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
• Objective response rate [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
• The number of patients with adverse events [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate whether overall survival for the trabectedin group is superior to the dacarbazine group for patients with advanced L-sarcoma (liposarcoma or leiomyosarcoma).

This is a randomized study (study drug assigned by chance) using a 2:1 randomization. It is an open-label (all patients and study staff know the identity of the assigned study drug), active-controlled (comparing to a different drug used for the same condition), parallel-group (different treatment groups continue with separate treatments throughout the study), multicenter study. This study will be divided into three phases, screening, treatment, and follow-up. During screening, potential patients will be assessed for study eligibility after providing signed informed consent. Approximately 570 patients who satisfy all inclusion and exclusion criteria will be randomly assigned in a 2:1 ratio to either the trabectedin (n=380) or dacarbazine (n=190) treatment groups. During the treatment phase, patients will receive study drug once every 3 weeks, until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1 criteria) or signs of toxicity. Assessments will be performed to evaluate the effectiveness of the drug, and patient safety will be monitored. During the follow-up phase, after the last dose of study drug, clinical outcomes for patients will be evaluated. Trabectedin will be administered at a dose of 1.5 mg/m2 through a catheter into a large vein as a 24-hour intravenous (IV) infusion, once every 3 weeks, until disease progression or signs of toxicity. Dacarbazine will be administered at a dose of 1.0 g/m2 as a 20-120 minute infusion, once every 3 weeks, until disease progression or signs of toxicity.

• Drug: Trabectedin
  Type=exactly number, unit=mg/m2, number=1.5, form=intravenous infusion, route=intravenous use. Once every 3 weeks until disease progression or signs of toxicity.
• Drug: Dacarbazine
  Type=exactly number, unit=g/m2, number=1, form=intravenous infusion, route=intravenous use. Once every 3 weeks until disease progression or signs of toxicity.

• Experimental: Trabectedin
  Intervention: Drug: Trabectedin
• Active Comparator: Dacarbazine
  Intervention: Drug: Dacarbazine

Inclusion Criteria:

• Locally advanced or spreading liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma.
• Treated in any order with at least an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen.
• Measurable disease at baseline in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
• Pathology specimens (eg, tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

• Prior exposure to trabectedin or dacarbazine.
• Less than 3 weeks from last dose of systemic cytotoxic therapy, radiation therapy, or therapy with any investigational agent.
• Other malignancy within past 3 years (exceptions: basal or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage 1 carcinoma of the cervix).
• Known central nervous system metastasis.
• Significant chronic liver disease, such as cirrhosis or active viral hepatitis.
• Heart attack within 6 months before enrollment.
• Any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.