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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01343277




Registration number
NCT01343277
Ethics application status
Date submitted
26/04/2011
Date registered
28/04/2011
Date last updated
26/08/2016

Titles & IDs
Public title
A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma
Scientific title
A Randomized Controlled Study of YONDELIS (Trabectedin) or Dacarbazine for the Treatment of Advanced Liposarcoma or Leiomyosarcoma
Secondary ID [1] 0 0
ET743SAR3007
Secondary ID [2] 0 0
CR018004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Liposarcoma or Leiomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trabectedin
Treatment: Drugs - Dacarbazine

Experimental: Trabectedin -

Active Comparator: Dacarbazine -


Treatment: Drugs: Trabectedin
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.

Treatment: Drugs: Dacarbazine
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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - 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.
Timepoint [1] 0 0
approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - 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.
Timepoint [1] 0 0
approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])
Secondary outcome [2] 0 0
Time to Progression - 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.
Timepoint [2] 0 0
approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])
Secondary outcome [3] 0 0
Objective Response Rate - 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.
Timepoint [3] 0 0
approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])
Secondary outcome [4] 0 0
Duration of Response - 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.
Timepoint [4] 0 0
approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])
Secondary outcome [5] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - 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.
Timepoint [5] 0 0
approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015])

Eligibility
Key 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
Minimum age
15 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Malvern
Recruitment hospital [2] 0 0
- Randwick
Recruitment hospital [3] 0 0
- Subiaco
Recruitment hospital [4] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
- Malvern
Recruitment postcode(s) [2] 0 0
- Randwick
Recruitment postcode(s) [3] 0 0
- Subiaco
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
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Georgia
Country [8] 0 0
United States of America
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Idaho
Country [9] 0 0
United States of America
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Illinois
Country [10] 0 0
United States of America
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Indiana
Country [11] 0 0
United States of America
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Iowa
Country [12] 0 0
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Kansas
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Kentucky
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Louisiana
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United States of America
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Maryland
Country [16] 0 0
United States of America
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Massachusetts
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United States of America
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Michigan
Country [18] 0 0
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Mississippi
Country [19] 0 0
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Missouri
Country [20] 0 0
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Nebraska
Country [21] 0 0
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Nevada
Country [22] 0 0
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New Hampshire
Country [23] 0 0
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
Country [28] 0 0
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Oklahoma
Country [29] 0 0
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Oregon
Country [30] 0 0
United States of America
State/province [30] 0 0
Pennsylvania
Country [31] 0 0
United States of America
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South Carolina
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Tennessee
Country [33] 0 0
United States of America
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Texas
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Utah
Country [35] 0 0
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Virginia
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Washington
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West Virginia
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Wisconsin
Country [39] 0 0
Brazil
State/province [39] 0 0
Bahia
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Brazil
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Barretos
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Brazil
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Ijuí
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Brazil
State/province [42] 0 0
Porto Alegre
Country [43] 0 0
Brazil
State/province [43] 0 0
Sao Paulo
Country [44] 0 0
Brazil
State/province [44] 0 0
São Paulo
Country [45] 0 0
New Zealand
State/province [45] 0 0
Auckland
Country [46] 0 0
New Zealand
State/province [46] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PharmaMar
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT01343277
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications