An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)

This study has been completed.
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00796120
First received: November 20, 2008
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention Phase
Sarcoma
Drug: Trabectedin
Drug: Doxorubicin
Drug: Ifosfamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Progression - Free Survival (PFS) [ Time Frame: Every 6 weeks from randomization during the first 9 months and thereafter, every 9 weeks up to 20 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 6 weeks during first 9 months of the study and thereafter every 9 weeks up to 20 months ] [ Designated as safety issue: No ]
    Tumor response was assessed according to 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 [ Time Frame: Baseline up to End of Study (an average of 4 years) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 20 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 121
Study Start Date: November 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trabectedin
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.
Drug: Trabectedin
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.
Active Comparator: Doxorubicin plus Ifosfamide
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.
Drug: Doxorubicin
Doxorubicin 60 or 75 mg/m^2 will be given intravenously every 3 weeks until disease progression.
Drug: Ifosfamide
Ifosfamide 6 to 9 g/m^2 will be given intravenously every 3 weeks until disease progression.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796120

Locations
United States, California
Santa Monica, California, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
France
Boreaux, France
Lille, France
Lyon, France
Paris, France
Villejuif, France
Germany
Bad Saarow, Germany
Köln, Germany
Mannheim, Germany
Spain
Barcelona, Spain
Palma De Mallorca N/A, Spain
Valencia N/A, Spain
United Kingdom
Edinburgh, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
PharmaMar
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, LLC Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00796120     History of Changes
Other Study ID Numbers: CR015769, ET-C-002-07
Study First Received: November 20, 2008
Results First Received: March 25, 2014
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Sarcomas
Trabectedin
Doxorubicin
Ifosfamide
YONDELIS

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Isophosphamide mustard
Trabectedin
Ifosfamide
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 18, 2014