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

NCT01189253 | Terminated Phase 2

• 5 other identifiers: EORTC-620912009-014889-26EU-21059PMAR-EORTC-62091SARC-020
• Study Type: interventional
• Target: 133
• Locations: 13 countries
• Sites: 43

Brief Summary

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.

Conditions

Sarcoma

Keywords

stage III adult soft tissue sarcoma; stage IV adult soft tissue sarcoma; adult alveolar soft-part sarcoma; adult angiosarcoma; adult desmoplastic small round cell tumor; adult epithelioid sarcoma; adult extraskeletal chondrosarcoma; adult extraskeletal osteosarcoma; adult fibrosarcoma; adult leiomyosarcoma; adult malignant fibrous histiocytoma; adult malignant hemangiopericytoma; adult malignant mesenchymoma; adult neurofibrosarcoma; adult synovial sarcoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival as assessed by RECIST v 1.1 criteria (phase IIB and phase III)

• Safety (phase IIB)

Secondary Outcomes (4)

• Overall survival (phase III)

• Response rate and response duration (phase III)

• Safety profile (phase III)

• Quality of life (phase III)

Study Arms (3)

Doxorubicin 75 mg/m² every 3 weeks

ACTIVE COMPARATOR

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

Drug: doxorubicin hydrochloride; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Trabectedin IV 3 hours

EXPERIMENTAL

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

Drug: trabectedin; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Trabectedin IV 24 hours every 3 weeks

EXPERIMENTAL

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

Drug: trabectedin; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Interventions

doxorubicin hydrochloride DRUG

Doxorubicin 75 mg/m² every 3 weeks

trabectedin DRUG

Trabectedin IV 24 hours every 3 weeks; Trabectedin IV 3 hours

laboratory biomarker analysis OTHER

Doxorubicin 75 mg/m² every 3 weeks; Trabectedin IV 24 hours every 3 weeks; Trabectedin IV 3 hours

quality-of-life assessment PROCEDURE

Doxorubicin 75 mg/m² every 3 weeks; Trabectedin IV 24 hours every 3 weeks; Trabectedin IV 3 hours

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed intermediate- or high-grade malignant soft tissue sarcoma * Advanced and/or metastatic disease * Previously untreated disease * The following tumor types are not allowed: * Well-differentiated liposarcoma * Embryonal rhabdomyosarcoma * Chondrosarcoma (excluding extraskeletal myxoid chondrosarcoma) * Osteosarcoma (excluding extraskeletal osteosarcoma) * Ewing tumors/primitive neuroectodermal tumor (PNET) * Gastrointestinal stromal tumors (GIST) * Dermatofibrosarcoma protuberans * Must have confirmed disease progression based on investigator's judgment prior to study enrollment * Measurable disease according to RECIST v 1.1 criteria * Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion * Formalin fixed paraffin embedded tumor blocks or representative hematoxylin/eosin slides (preferably both) available (local histopathological diagnosis will be accepted for trial entry) * No prior anticancer therapy for this disease * No prior anthracycline * Non-anthracycline therapy for nonmetastatic disease is acceptable * No known history of CNS metastases or leptomeningeal tumor spread PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100 x 10\^9/L * Bilirubin normal * ALT/AST ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN, (if alkaline phosphatase \> 2.5 times ULN, hepatic isoenzymes 5-nucleotidase and/or GGT must be within the normal range) * Albumin \> 30 g/L * Serum creatinine ≤ 1.5 times ULN * Creatinine clearance ≥ 30 mL/min * Creatine phosphokinase (CPK) ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception (double barrier method for men) 2 weeks prior to, during, and for 3 months (women) or 5 months (men) after completion of study therapy * LVEF normal by MUGA scan or ECHO * 12-lead ECG normal (without clinically significant abnormalities) * None of the following unstable cardiac conditions: * Congestive heart failure * Angina pectoris * Myocardial infarction within the past year * Uncontrolled arterial hypertension, defined as BP ≥ 150/100 mm Hg despite optimal medical therapy * Clinically significant arrhythmias * No active or uncontrolled infections or serious illnesses or medical conditions, including a history of any of the following: * Chronic alcohol abuse * Hepatitis * HIV * Cirrhosis * No history of malignancy within the past 5 years, except soft tissue sarcoma, basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 with Gleason score ≤ 6 and postoperative PSA \< 0.5 ng/mL) * Patients with any history of malignancies who are disease-free for more than 5 years are eligible * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Sarcoma Alliance for Research through Collaboration: collaborator

Study Sites (43)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Stanford Hospital and Clinics

Stanford, California, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Dana Farber Institute

Boston, Massachusetts, 02115, United States

Location

Massachussets General Hospital

Boston, Massachusetts, United States

Location

Methodist Estabrook Cancer Center

Omaha, Nebraska, 68114-4199, United States

Location

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, 28203-4239, United States

Location

Pennsylvania Oncology Hematology Associates, Incorporated - Philadelphia

Philadelphia, Pennsylvania, 19106, United States

Location

Medical University Vienna

Vienna, 1090, Austria

Location

HôPITAUX UNIVERSITAIRES BORDET-ERASME - INSTITUT JULES BORDET

Brussels, 1000, Belgium

Location

Cliniques Universitaires St. Luc

Brussels, 1200, Belgium

Location

U.Z. Gasthuisberg

Leuven, 3000, Belgium

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Herlev Hospital - University Copenhagen

Herlev, 2730, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Georges-Francois-Leclerc

Dijon, 77980, France

Location

Centre Oscar Lambret

Lille, B.P. 307, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

ASSISTANCE PUBLIQUE - HôPITAUX DE MARSEILLE - HôPITAL DE LA TIMONE

Marseille, 13385, France

Location

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

Nantes - Saint Herblain, 44805, France

Location

Institut Curie

Paris, 75231, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Universitaetsklinikum Koeln

Cologne, 50924, Germany

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitaets-Krankenhaus Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsmedizin Mannheim

Mannheim, 68167, Germany

Location

Klinikum Grosshadern Ludwig-Maximilians Univ. Muenchen

München, 81377, Germany

Location

Military Hospital - State Health Centre

Budapest, 1063, Hungary

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, 1066, Netherlands

Location

University Medical Center Groningen

Groningen, 9700, Netherlands

Location

Leiden University Medical Centre

Leiden, 2300, Netherlands

Location

Radboud University Nijmegen Medical Centre

Nijmegen, 6500, Netherlands

Location

Erasmus Mc - Daniel Den Hoed Cancer Center

Rotterdam, 3008, Netherlands

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, 02 781, Poland

Location

National Cancer Institute

Bratislava, 83310, Slovakia

Location

Hospital General Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario San Carlos

Madrid, 28040, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

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

Glasgow, G12 0YN, United Kingdom

Location

Christie Nhs Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals Nhs Trust - City Hospital Campus

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma; Sarcoma, Alveolar Soft Part; Hemangiosarcoma; Desmoplastic Small Round Cell Tumor; Chondrosarcoma, Extraskeletal Myxoid; Fibrosarcoma; Leiomyosarcoma; Histiocytoma, Malignant Fibrous; Hemangiopericytoma, Malignant; Malignant mesenchymal tumor; Neurofibrosarcoma; Sarcoma, Synovial

Interventions

Doxorubicin; Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Neoplasms, Vascular Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Histiocytoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nguyen Binh Bui, MD

  Institut Bergonié

  STUDY CHAIR

• James E. Butrynski, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 26, 2010
• Study Start: May 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2015
• Last Updated: August 8, 2014

Record last verified: 2013-08

Locations

HU (1); US (8); NL (5); ES (2); AU (1); SL (1); CH (1); GB (3); DE (7); DK (2); BE (3); FR (8); PL (1)