A Randomized Controlled Study of YONDELIS (Trabectedin) or Dacarbazine for the Treatment of Advanced Liposarcoma or Leiomyosarcoma Previously Treated with an Anthracycline and Ifosfamide
This is a randomized, open-label, active-controlled, parallel-group, multicenter study comparing the safety
and efficacy of trabectedin with dacarbazine among adults with unresectable, locally advanced or
metastatic L-sarcoma, who were previously treated with an anthracycline and ifosfamide. The intent of the
study is to determine whether trabectedin treatment is superior to dacarbazine treatment with regard to OS.
During the Screening Phase, potential subjects will be assessed for study eligibility after providing
informed consent to participate in the study. Baseline radiographic disease assessments must be performed
within 30 days before randomization. Approximately 570 subjects 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. Before randomization, subjects will be stratified by the number of lines of prior
chemotherapy (1 versus 2 or more), Eastern Cooperative Oncology Group (ECOG) Performance Status
score (0 versus 1), and L-sarcoma subtype (liposarcoma versus leiomyosarcoma).
During the Treatment Phase, subjects will receive study drug on Day 1 of each 21-day cycle. A subject will
continue to receive study drug until there is documented disease progression or unacceptable toxicity.
Disease response will be assessed using Response Evaluation Criteria in Solid Tumors
(RECIST Version 1.1) guidelines. Radiographic assessment of disease will be performed every 6 weeks for
the first 36 weeks on study and every 9 weeks thereafter, until disease progression occurs, the subject
begins subsequent anticancer therapy, the study ends, or the subject dies. Subsequent therapy should only
be started after disease progression has been documented. All adverse events that occur from the time a
subject provides signed informed consent until 30 days after his or her last dose of study drug will be
During the Follow-up Phase, subjects will be monitored for survival status and the start of subsequent
anticancer therapy at least every 60 days for the first 2 years after the last dose of study drug and every
90 days thereafter, until approximately 376 deaths have been observed. Subjects who discontinue study
drug before disease progression occurs (eg, subjects who discontinue treatment due to unacceptable
toxicity) will continue to have radiographic assessments of disease, as described above.
15 years of age or older at time of screening; (UT Southwestern will enroll subjects age 18 and older. )
Histologically proven, unresectable, locally advanced or metastatic liposarcoma
(dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Subjects
must have a pathology report indicating the diagnosis of liposarcoma or
leiomyosarcoma that has been reviewed by the sponsor before randomization may
Treated in any order with at least: a) with an anthracycline and ifosfamide administered regimen or b) an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen.
Measurable disease at baseline in accordance with RECIST Version 1.1
Pathology specimens (eg, 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 g/dL
– absolute neutrophil count (ANC) ≥1,500/mL
– platelet count ≥100,000/mL
– serum creatinine ≤1.5 x the upper limit of normal (ULN)
– creatine phosphokinase (CPK) ≤2.5 x ULN.
Adequate hepatic function as evidenced by the following serum chemistry values:
– total bilirubin ≤ ULN. If total bilirubin is > ULN, measure indirect bilirubin to
evaluate for Gilbert’s syndrome (if direct bilirubin is within normal range, subject
may be eligible).
– ALP ≤2.5 x ULN; if ALP is >2.5 x ULN, then an ALP liver fraction or 5’ nucleotidase must be obtained and ≤ ULN
– AST and ALT ≤2.5 x ULN.
Negative pregnancy test (urinary or serum β-HCG) at screening (applicable to women
of child bearing potential who are sexually active)
Female subjects 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 (eg., prescription hormonal contraceptive, intrauterine device, double-barrier method [eg, condoms and occlusive cap (diaphragm or cervical/vault caps)] with spermicidal foam, cream, gel, file, suppository), before entry and must agree to continue to use the same method of contraceptive throughout the study and for 3 months thereafter.
Male subjects must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not
donate sperm for a minimum of 5 months after treatment discontinuation.
Signed informed consent document indicating they understand the purpose of and the
procedures required for the study and are willing to participate in the study.