A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma
Condition: Advanced Liposarcoma or Leiomyosarcoma
MeSH terms: Leiomyosarcoma; Liposarcoma
Intervention: Trabectedin; Dacarbazine
Intervention description: 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.; 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.
Intervention MeSH terms: Dacarbazine; Trabectedin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 579.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Advanced Liposarcoma or Leiomyosarcoma; Trabectedin; Yondelis; Dacarbazine; Anthracycline; L-sarcoma

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven, unresectable, locally advanced or metastatic liposarcoma
             (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Participants
             must have a pathology report indicating the diagnosis of liposarcoma or leiomyosarcoma
             that has been reviewed by the sponsor before randomization may occur

          -  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 RECIST Version 1.1

          -  Pathology specimens (example [e.g.], tumor blocks or unstained slides) for potential
             centralized pathology review and biomarker studies

          -  ECOG Performance Status score of 0 or 1

          -  Adequate recovery from prior therapy, all side effects (except alopecia) have resolved
             to Grade 1 or less according to the National Cancer Institute - Common Terminology
             Criteria of Adverse Events (NCI-CTCAE) Version 4.0

          -  Adequate organ function as evidenced by the following peripheral blood counts or serum
             chemistry values: hemoglobin 9 gram per deciliters (g/dL), absolute neutrophil count
             (ANC) 1,500/L, platelet count 100,000/L, serum creatinine 1.5*the upper limit of
             normal (ULN), creatine phosphokinase (CPK) 2.5 Upper Limit of Normal [ULN]

          -  Adequate hepatic function as evidenced by the following serum chemistry values: total
             bilirubin, ULN. If total bilirubin is greater than (>) ULN, measure indirect bilirubin
             to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range,
             participant may be eligible) ALP 2.5 x ULN; Trabectedin: if the ALP is >2.5 x ULN,
             then an ALP liver fraction or 5-nucleotidase must be obtained and ULN, AST and ALT 2.5
             ULN

          -  Negative pregnancy test (urinary or serum beta-HCG) at screening (applicable to women
             of child bearing potential who are sexually active)

          -  Female participants must be postmenopausal (no spontaneous menses for at least 2
             years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal
             ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the
             investigator), or if sexually active, be practicing an effective method of birth
             control. Male participants must agree to use an adequate contraception method as
             deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using
             effective contraception) and to not donate sperm for a minimum of 5 months after
             treatment discontinuation

        Optional Extension Phase (OEP) Phase:

          -  Documentation for inclusion criteria histologically proven, unresectable, locally
             advanced or metastatic liposarcoma (dedifferentiated, myxoid round cell, or
             pleomorphic) or leiomyosarcoma. Participants must have a pathology report indicating
             the diagnosis of liposarcoma or leiomyosarcoma that has been reviewed by the sponsor
             before randomization may occur and treated in any order with at least: an
             anthracycline and ifosfamide containing regimen, or an anthracycline containing
             regimen and 1 additional cytotoxic chemotherapy regimen do not need to be reviewed by
             the Sponsor

          -  Collection of the specimen: Pathology specimens (example (e.g.), tumor blocks or
             unstained slides) for potential centralized pathology review and biomarker studies is
             not applicable

          -  Documentation of inclusion criteria adequate organ function as evidenced by the
             following peripheral blood counts or serum chemistry values: hemoglobin 9 gram per
             deciliters (g/dL), absolute neutrophil count (ANC) 1,500/L, platelet count 100,000/L,
             serum creatinine 1.5*the upper limit of normal (ULN), creatine phosphokinase (CPK)
             2.5*ULN and adequate hepatic function as evidenced by the following serum chemistry
             values: total bilirubin, ULN. If total bilirubin is greater than (>) ULN, measure
             indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within
             normal range, participant may be eligible) ALP <= 2.5*ULN; Trabectedin: if the ALP is
             >2.5*ULN, then an ALP liver fraction or 5-nucleotidase must be obtained and ULN, AST
             and ALT 2.5 ULN will be reviewed by the Sponsor before enrollment in the OEP may occur

        Exclusion Criteria:

          -  Potential participants who meet any of the following criteria will be excluded from
             participating in the study: Prior exposure to trabectedin or dacarabazine, 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

          -  Known significant chronic liver disease, such as cirrhosis or active hepatitis
             (potential participants who test positive for hepatitis B surface antigen or hepatitis
             C antibodies are allowed provided they do not have active disease requiring antiviral
             therapy)

          -  Myocardial infarct within 6 months before enrollment, New York Heart Association Class
             II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular
             arrhythmias, clinically significant pericardial disease, or electrocardiographic
             evidence of acute ischemic or active conduction system abnormalities

          -  Uncontrolled intercurrent illness including, but not limited to, poorly controlled
             hypertension or diabetes, ongoing active infection, or psychiatric illness/social
             situation that may potentially impair the participant's compliance with study
             procedures

          -  Unwilling or unable to have a central venous catheter

          -  Known allergies, hypersensitivity, or intolerance to trabectedin, dacarbazine,
             dexamethasone, or their excipients

          -  Pregnant or breast-feeding

          -  Any condition that, in the opinion of the investigator, would compromise the
             well-being of the participant or the study or prevent the participant from meeting or
             performing study requirements

        OEP phase:

          -  Potential participants who meet any of the following criteria will be excluded from
             Participating in the study: Prior exposure to trabectedin, 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 does not apply

          -  Treated in any order with at least: an anthracycline and ifosfamide containing
             regimen, or an anthracycline containing regimen and 1 additional cytotoxic
             chemotherapy regimen with less than 3 weeks from last dose of systemic anticancer
             therapy, radiation therapy, or therapy with any investigational agent

          -  Known allergies, hypersensitivity, or intolerance to dacarbazine does not apply