Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma

NCT ID: NCT01189253

Last Updated: 2014-08-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2015-06-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride and trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether trabectedin is more effective than doxorubicin hydrochloride in treating patients with advanced or metastatic soft tissue sarcoma.

PURPOSE: This randomized phase II/III trial is studying the safety of trabectedin compared with doxorubicin hydrochloride and to see how well they work in treating patients with advanced or metastatic soft tissue sarcoma.

Detailed Description

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OBJECTIVES:

* To evaluate whether trabectedin given as first-line chemotherapy for patients with previously untreated advanced or metastatic malignant soft tissue sarcoma prolongs progression-free survival as compared to doxorubicin hydrochloride.
* To identify and validate biomarkers (including, but not limited to, XPG, BRCA1, RAD51, BRCA2, ATM and CHK1) of sensitivity to trabectedin in order to allow the selection of patients that benefit most from trabectedin treatment. (Optional translational research)

OUTLINE: This is a multicenter, phase IIB study followed by a phase III study. Patients are stratified according to institution, age at registration (\< 60 years old vs ≥ 60 years old), and presence of liver metastases (yes vs no).

* Phase IIB (step 1): Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive trabectedin IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive trabectedin IV continuously over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

At the end of step 1, the best regimen of trabectedin will be determined. Patients receiving the non-selected trabectedin regimen ("losing arm") are offered to cross over in order to receive the selected regimen of trabectedin.

* Phase III (step 2): Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive trabectedin IV on day 1 using the preferred regimen determined in step 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaire (EORTC QLQ-C30 version 3) at baseline, at 6, 12, 24, and 36 weeks during study, and at the end of study.

Tumor tissue block obtained at diagnosis may be analyzed to identify and validate biomarkers of sensitivity to trabectedin and for tissue microarrays.

After completion of study therapy, patients are followed up at 1 month, every 6 or 12 weeks until disease progression, and every 12 weeks thereafter.

Conditions

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Sarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Doxorubicin 75 mg/m² every 3 weeks

Doxorubicin administered on day 1 every 3 weeks for a maximum of 6 cycles

Group Type ACTIVE_COMPARATOR

doxorubicin hydrochloride

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Trabectedin IV 3 hours

Trabectedin administered on day 1 every 3 weeks at the dose of 1.3 mg/m² until progression

Group Type EXPERIMENTAL

trabectedin

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Trabectedin IV 24 hours every 3 weeks

Trabectedin administered on day 1 every 3 weeks at the dose of 1.5 mg/m² over 24 hours until progression

Group Type EXPERIMENTAL

trabectedin

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Interventions

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doxorubicin hydrochloride

Intervention Type DRUG

trabectedin

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* a history of malignancy and disease-free for more than 5 years
* No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* No concurrent alcohol consumption

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 28 days since prior and no concurrent anticancer therapy including systemic therapy, radiotherapy, or surgery
* At least 28 days since prior and no other concurrent investigational agents
* No concurrent phenytoin, live attenuated vaccines, or yellow fever vaccine
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sarcoma Alliance for Research through Collaboration

OTHER

Sponsor Role collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nguyen Binh Bui, MD

Role: STUDY_CHAIR

Institut Bergonié

James E. Butrynski, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Sarcoma Oncology Center

Santa Monica, California, United States

Site Status

Stanford Hospital and Clinics

Stanford, California, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Dana Farber Institute

Boston, Massachusetts, United States

Site Status

Massachussets General Hospital

Boston, Massachusetts, United States

Site Status

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

Site Status

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, United States

Site Status

Pennsylvania Oncology Hematology Associates, Incorporated - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University Vienna

Vienna, , Austria

Site Status

HôPITAUX UNIVERSITAIRES BORDET-ERASME - INSTITUT JULES BORDET

Brussels, , Belgium

Site Status

Cliniques Universitaires St. Luc

Brussels, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Herlev Hospital - University Copenhagen

Herlev, , Denmark

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Centre Georges-Francois-Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

ASSISTANCE PUBLIQUE - HôPITAUX DE MARSEILLE - HôPITAL DE LA TIMONE

Marseille, , France

Site Status

Institut de Cancerologie de L'Ouest (Ico) - Centre Rene Gauducheau

Nantes - Saint Herblain, , France

Site Status

Institut Curie

Paris, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Site Status

Universitaetsklinikum Koeln

Cologne, , Germany

Site Status

Universitaetsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status

Universitaets-Krankenhaus Eppendorf

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitaetsmedizin Mannheim

Mannheim, , Germany

Site Status

Klinikum Grosshadern Ludwig-Maximilians Univ. Muenchen

München, , Germany

Site Status

Military Hospital - State Health Centre

Budapest, , Hungary

Site Status

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Leiden University Medical Centre

Leiden, , Netherlands

Site Status

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Site Status

Erasmus Mc - Daniel Den Hoed Cancer Center

Rotterdam, , Netherlands

Site Status

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, , Poland

Site Status

National Cancer Institute

Bratislava, , Slovakia

Site Status

Hospital General Vall D'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario San Carlos

Madrid, , Spain

Site Status

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Site Status

Nhs Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Christie Nhs Foundation Trust

Manchester, , United Kingdom

Site Status

Nottingham University Hospitals Nhs Trust - City Hospital Campus

Nottingham, , United Kingdom

Site Status

Countries

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United States Austria Belgium Denmark France Germany Hungary Netherlands Poland Slovakia Spain Switzerland United Kingdom

Other Identifiers

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EORTC-62091

Identifier Type: -

Identifier Source: secondary_id

2009-014889-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EU-21059

Identifier Type: -

Identifier Source: secondary_id

PMAR-EORTC-62091

Identifier Type: -

Identifier Source: secondary_id

SARC-020

Identifier Type: -

Identifier Source: secondary_id

EORTC-62091

Identifier Type: -

Identifier Source: org_study_id

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