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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Controlled Study of YONDELIS (Trabectedin) or Dacarbazine for the Treatment of Advanced Liposarcoma or Leiomyosarcoma

Brief 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).

Detailed Summary: 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.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: Overall Survival (OS) [ Time Frame: approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015] ]

Original Primary Outcome: Evaluation of overall survival [ Time Frame: Approximately 3 years ]

Current Secondary Outcome:

• Progression-Free Survival (PFS) [ Time Frame: approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) ]
  The Progression-Free Survival (PFS) was assessed as median number of months from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
• Time to Progression [ Time Frame: approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) ]

  Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.

  Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.

• Objective Response Rate [ Time Frame: approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) ]
  The objective response rate (ORR) is defined as the percentage of participants who achieved a Complete response (CR) or partial response (PR) as best responses. according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
• Duration of Response [ Time Frame: approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) ]

  Duration of response is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.

  Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]) ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Original Secondary Outcome:

• Progression-free survival [ Time Frame: Approximately 3 years ]
• Time to Progression [ Time Frame: Approximately 3 years ]
• Objective Response Rate [ Time Frame: Approximately 3 years ]
• Duration of Response [ Time Frame: Approximately 3 years ]
• The number of patients with adverse events [ Time Frame: Approximately 3 years ]

Dates:
Date Received: April 26, 2011
Date Started: June 2011
Date Completion:
Last Updated: July 15, 2016
Last Verified: July 2016