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

Trial Status: Complete

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).

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

Arizona

Tucson
Banner University Medical Center - Tucson
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: COMPLETED
USC / Norris Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Palo Alto
Stanford Cancer Institute Palo Alto
Status: COMPLETED
San Francisco
UCSF Medical Center-Mount Zion
Status: CLOSED_TO_ACCRUAL

Colorado

Aurora
University of Colorado Hospital
Status: COMPLETED

Connecticut

New Haven
Yale University
Status: COMPLETED

Florida

Tampa
Moffitt Cancer Center
Status: COMPLETED

Illinois

Chicago
Northwestern University
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: COMPLETED

Kansas

Overland Park
University of Kansas Cancer Center-Overland Park
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Massachusetts

Boston
Brigham and Women's Hospital
Status: CLOSED_TO_ACCRUAL
Dana-Farber Cancer Institute
Status: CLOSED_TO_ACCRUAL
Massachusetts General Hospital Cancer Center
Status: COMPLETED

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: COMPLETED

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: COMPLETED

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: CLOSED_TO_ACCRUAL

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: COMPLETED

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: CLOSED_TO_ACCRUAL
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL
Memorial Sloan Kettering Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: COMPLETED

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Durham
Duke University Medical Center
Status: WITHDRAWN

Ohio

Cleveland
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Columbus
Ohio State University Comprehensive Cancer Center
Status: COMPLETED

Oregon

Portland
OHSU Knight Cancer Institute
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: CLOSED_TO_ACCRUAL
University of Pennsylvania / Abramson Cancer Center
Status: COMPLETED
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: CLOSED_TO_ACCRUAL

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Houston
M D Anderson Cancer Center
Status: COMPLETED
San Antonio
University of Texas Health Science Center at San Antonio
Status: COMPLETED

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

This is a randomized study (study drug assigned by chance) using a 2:1 randomization. It is an open-label (all people know 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 3 phases, screening, treatment, follow-up and optional extension phase (OEP). During screening, potential participants 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 milligram per square meters (mg/m^2) 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/m^2 as a 20-120 minute infusion, once every 3 weeks, until disease progression or signs of toxicity. In the OEP, participants who were previously randomized to the dacarbazine group will have the option to receive trabectedin at the discretion of the investigator.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Janssen Pharmaceuticals

  • Primary ID CR018004
  • Secondary IDs NCI-2011-01162, ET743SAR3007, S12-01251
  • Clinicaltrials.gov ID NCT01343277