Trial Outcomes & Findings for A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma (NCT NCT01343277)

Last Updated: 2016-08-26

Results Overview

The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

579 participants

Primary outcome timeframe

approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]

Results posted on

2016-08-26

Participant Flow

Total enrolled participants were 577, but 2 participants were randomized twice, therefore counted twice in enrollment. Thus, enrolled participants are reported as 579.

Participant milestones

Participant milestones
Measure	Trabectedin Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Overall Study STARTED	384	193
Overall Study Treated	378	172
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	384	193

Reasons for withdrawal

Reasons for withdrawal
Measure	Trabectedin Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Overall Study Other	3	3
Overall Study Withdrawal by Subject	18	13
Overall Study Physician Decision	1	2
Overall Study Death	10	1
Overall Study Adverse Event	67	13
Overall Study Disease progression	270	138
Overall Study Randomized not treated	6	21
Overall Study Treatment ongoing	8	2
Overall Study Subsequent anticancer therapy	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trabectedin n=384 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=193 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.	Total n=577 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 11.04 • n=5 Participants	54.1 years STANDARD_DEVIATION 11.92 • n=7 Participants	55.7 years STANDARD_DEVIATION 11.39 • n=5 Participants
Sex: Female, Male Female	262 Participants n=5 Participants	140 Participants n=7 Participants	402 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	53 Participants n=7 Participants	175 Participants n=5 Participants
Region of Enrollment AUS	15 participants n=5 Participants	8 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment BRA	10 participants n=5 Participants	2 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment NZL	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment USA	356 participants n=5 Participants	183 participants n=7 Participants	539 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]

Population: Analysis population included all the randomized participants up to up to final analysis cut-off date (05 January 2015).

Outcome measures

Outcome measures
Measure	Trabectedin n=384 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=193 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Overall Survival (OS)	13.73 Months Interval 12.16 to 16.0	13.14 Months Interval 9.1 to 16.23

SECONDARY outcome

Timeframe: approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])

Population: Analysis population included all the randomized participants up to interim analysis cut-off date (16 September 2013). "N" (number of participants analyzed) signifies the participants evaluable for this measure.

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.

Outcome measures

Outcome measures
Measure	Trabectedin n=345 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=173 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Progression-Free Survival (PFS)	4.21 Months Interval 2.99 to 4.83	1.54 Months Interval 1.48 to 2.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Trabectedin n=345 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=173 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Time to Progression	4.24 Months Interval 3.22 to 4.93	1.54 Months Interval 1.48 to 2.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Trabectedin n=345 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=173 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Objective Response Rate	9.9 Percentage of Participants Interval 6.9 to 13.5	6.9 Percentage of Participants Interval 3.6 to 11.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Trabectedin n=34 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=12 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Duration of Response	6.47 Months Interval 3.58 to 7.62	4.17 Months Interval 2.14 to Insufficient participants reached the median percentile to calculate the upper limits of confidence interval.

SECONDARY outcome

Timeframe: approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015])

Population: Safety population included all the treated participants.

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.

Outcome measures

Outcome measures
Measure	Trabectedin n=378 Participants Trabectedin at a dose of 1.5 milligram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion.	Dacarbazine n=172 Participants Dacarbazine at a dose of 1 gram per meter square (mg/m\^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events (SAEs)	155 Participants	52 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs)	375 Participants	166 Participants

Adverse Events

Trabectedin

Serious events: 155 serious events

Other events: 375 other events

Deaths: 0 deaths

Dacarbazine

Serious events: 52 serious events

Other events: 166 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director

Janssen Research & Development, LLC

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER