Back to resultsAn Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)
Primary Purpose
Sarcoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Trabectedin
Doxorubicin
Ifosfamide
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma focused on measuring Sarcomas, Trabectedin, Doxorubicin, Ifosfamide, YONDELIS
Eligibility Criteria
Inclusion Criteria:
- Pathological diagnosis of translocation-related sarcomas (TRS) including the following subtypes: alveolar soft part sarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, low grade endometrial stromal sarcoma (prior hormone therapy allowed), low grade fibromyxoid sarcoma, myxoid chondrosarcoma, myxoid/round cell liposarcoma (MRCL) and synovial sarcoma
- Participants must have unresectable locally advanced or metastatic progressive disease prior to enrolment
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) within normal limits according to institutional standards, as shown by echocardiography or scintigraphy multiple-gated acquisition scan [MUGA]
- Measurable disease as defined by the radiological (computed tomography [CT] scan and magnetic resonance imaging [MRI]) Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) guidelines
Exclusion Criteria:
- Known hypersensitivity to any components of the intravenous formulation of trabectedin or the comparators
- Prior chemotherapy treatment or irradiation of the lesion if only one target lesion is available
- Brain metastases and/or leptomeningeal metastases, even if treated
- Pregnant or lactating women or men and women of reproductive potential who are not using effective contraceptive methods
- History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for five years or more
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Trabectedin
Doxorubicin plus Ifosfamide
Arm Description
Trabectedin 1.5 milligram per square meter (mg/m^2) will be given as 24-hour continuous intravenous infusion every 3 weeks until disease progression.
Doxorubicin (as a monotherapy) 75 mg per m^2 will be given intravenously every 3 weeks or Doxorubicin 60 mg per m^2 will be given intravenously every 3 weeks followed by ifosfamide 6 to 9 gram (g)/m^2 every 3 weeks until disease progression.
Outcomes
Primary Outcome Measures
Progression - Free Survival (PFS)
The PFS was assessed as median number of days from the date of randomization until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
Secondary Outcome Measures
6-month Progression - Free Survival
Percentage of participants survived for 6 months from the start of study treatment without progression of disease. Progression of the disease was associated with increasing symptoms, including pain from new or progressing lesions. Delay in disease progression generally represents a clinical benefit to the participant.
Percentage of Participants With Objective Response
Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Partial Response (PR)=at least 30% reduction in the sum of the longest dimensions (LD) of all target lesions in reference to the baseline sum LD, Complete Response (CR) =Disappearance of all non-target lesions. Percentage of participants with objective tumor response was determined by the number of participants with PR or CR divided by the total number of response-evaluable participants.
Overall Survival
Overall survival defined as time from the date of randomization to the date of death. For participants who were alive at the time of analysis, overall survival was censored at the last contact date.
Duration of Response (DOR)
The DOR is defined as the time from date of first documentation of response (CR or PR, whichever comes first) to the date of documented PD or death. PR=at least 30% reduction in the sum of the longest dimensions (LD) of all target lesions in reference to the baseline sum LD, CR =Disappearance of all non-target lesions.
Full Information
NCT ID
NCT00796120
First Posted
November 20, 2008
Last Updated
December 9, 2015
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Collaborators
PharmaMar
1. Study Identification
Unique Protocol Identification Number
NCT00796120
Brief Title
An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)
Official Title
A Randomized, Multicenter, Phase III Trial of Trabectedin (Yondelis) Versus Doxorubicin-based Chemotherapy as First-Line Therapy in Patients With Translocation-Related Sarcomas (TRS)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Collaborators
PharmaMar
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of trabectedin compared to standard doxorubicin in participants with advanced translocation-related sarcomas (cancer of connective tissue cells) (TRS).
Detailed Description
This is a randomized (study drug assigned by chance), multicenter (when more than one hospital or medical school team work on a medical research study), Phase 3 trial to evaluate the efficacy and safety of trabectedin as compared to standard doxorubicin in participants with advanced TRS. Participants will be randomized in a 1:1 ratio to either of the 2 treatment groups, that is, trabectedin or doxorubicin plus ifosfamide group. Participants in trabectedin group will receive trabectedin 1.5 milligram per square meter (mg/m^2) given as a 24-hour continuous intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) every 3 weeks and in doxorubicin plus ifosfamide group participants will receive doxorubicin 60 or 75 mg/m^2 intravenously every 3 weeks followed by ifosfamide 6 to 9 gram (g)/m^2 every 3 weeks. Participants in either treatment arm will continue receiving therapy in the absence of progressive disease (PD) or intolerable side effects, until the participants' consent is withdrawn or the eligibility criteria for continuing treatment are no longer fulfilled, or when a concurrent condition precludes continuation of treatment. Efficacy will be assessed primarily by evaluating progression-free survival (PFS). Participants' safety will be monitored throughout the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
Sarcomas, Trabectedin, Doxorubicin, Ifosfamide, YONDELIS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trabectedin
Arm Type
Experimental
Arm Description
Trabectedin 1.5 milligram per square meter (mg/m^2) will be given as 24-hour continuous intravenous infusion every 3 weeks until disease progression.
Arm Title
Doxorubicin plus Ifosfamide
Arm Type
Active Comparator
Arm Description
Doxorubicin (as a monotherapy) 75 mg per m^2 will be given intravenously every 3 weeks or Doxorubicin 60 mg per m^2 will be given intravenously every 3 weeks followed by ifosfamide 6 to 9 gram (g)/m^2 every 3 weeks until disease progression.
Intervention Type
Drug
Intervention Name(s)
Trabectedin
Intervention Description
Trabectedin 1.5 milligram per square meter (mg/m^2) will be given as 24-hour continuous intravenous infusion every 3 weeks until disease progression.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Doxorubicin 60 or 75 mg/m^2 will be given intravenously every 3 weeks until disease progression.
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Intervention Description
Ifosfamide 6 to 9 g/m^2 will be given intravenously every 3 weeks until disease progression.
Primary Outcome Measure Information:
Title
Progression - Free Survival (PFS)
Description
The PFS was assessed as median number of days from the date of randomization until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
Time Frame
Every 6 weeks from randomization during the first 9 months and thereafter, every 9 weeks up to 20 months
Secondary Outcome Measure Information:
Title
6-month Progression - Free Survival
Description
Percentage of participants survived for 6 months from the start of study treatment without progression of disease. Progression of the disease was associated with increasing symptoms, including pain from new or progressing lesions. Delay in disease progression generally represents a clinical benefit to the participant.
Time Frame
6 months
Title
Percentage of Participants With Objective Response
Description
Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Partial Response (PR)=at least 30% reduction in the sum of the longest dimensions (LD) of all target lesions in reference to the baseline sum LD, Complete Response (CR) =Disappearance of all non-target lesions. Percentage of participants with objective tumor response was determined by the number of participants with PR or CR divided by the total number of response-evaluable participants.
Time Frame
Every 6 weeks during first 9 months of the study and thereafter every 9 weeks up to 20 months
Title
Overall Survival
Description
Overall survival defined as time from the date of randomization to the date of death. For participants who were alive at the time of analysis, overall survival was censored at the last contact date.
Time Frame
Baseline up to End of Study (an average of 4 years)
Title
Duration of Response (DOR)
Description
The DOR is defined as the time from date of first documentation of response (CR or PR, whichever comes first) to the date of documented PD or death. PR=at least 30% reduction in the sum of the longest dimensions (LD) of all target lesions in reference to the baseline sum LD, CR =Disappearance of all non-target lesions.
Time Frame
Up to 20 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathological diagnosis of translocation-related sarcomas (TRS) including the following subtypes: alveolar soft part sarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, low grade endometrial stromal sarcoma (prior hormone therapy allowed), low grade fibromyxoid sarcoma, myxoid chondrosarcoma, myxoid/round cell liposarcoma (MRCL) and synovial sarcoma
Participants must have unresectable locally advanced or metastatic progressive disease prior to enrolment
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) within normal limits according to institutional standards, as shown by echocardiography or scintigraphy multiple-gated acquisition scan [MUGA]
Measurable disease as defined by the radiological (computed tomography [CT] scan and magnetic resonance imaging [MRI]) Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) guidelines
Exclusion Criteria:
Known hypersensitivity to any components of the intravenous formulation of trabectedin or the comparators
Prior chemotherapy treatment or irradiation of the lesion if only one target lesion is available
Brain metastases and/or leptomeningeal metastases, even if treated
Pregnant or lactating women or men and women of reproductive potential who are not using effective contraceptive methods
History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for five years or more
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, LLC Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
Facility Information:
City
Santa Monica
State/Province
California
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Boreaux
Country
France
City
Lille
Country
France
City
Lyon
Country
France
City
Paris
Country
France
City
Villejuif
Country
France
City
Bad Saarow
Country
Germany
City
Köln
Country
Germany
City
Mannheim
Country
Germany
City
Barcelona
Country
Spain
City
Palma De Mallorca N/A
Country
Spain
City
Valencia N/A
Country
Spain
City
Edinburgh
Country
United Kingdom
City
Glasgow
Country
United Kingdom
City
London
Country
United Kingdom
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
24512981
Citation
Blay JY, Leahy MG, Nguyen BB, Patel SR, Hohenberger P, Santoro A, Staddon AP, Penel N, Piperno-Neumann S, Hendifar A, Lardelli P, Nieto A, Alfaro V, Chawla SP. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer. 2014 Apr;50(6):1137-47. doi: 10.1016/j.ejca.2014.01.012. Epub 2014 Feb 7.
Results Reference
derived
Learn more about this trial
An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)
We'll reach out to this number within 24 hrs