• Six-month progression-free survival, in terms of complete response, partial response, or no change [ Designated as safety issue: No ]
  

• Overall progression-free survival [ Designated as safety issue: No ]
  
• Objective tumor response [ Designated as safety issue: No ]
  
• Safety (CTCAE v 3.0) [ Designated as safety issue: Yes ]
  
• Duration of response [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the activity and safety of brostallicin vs doxorubicin hydrochloride as first-line therapy in patients with relapsed, refractory, or metastatic soft tissue sarcoma.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating and age(younger than 60 years vs 60 years and over). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive brostallicin IV over 10 minutes on day 1.
• Arm II: Patients receive doxorubicin hydrochloride IV over 10 minutes on day 1. In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 108 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed high- or intermediate-grade malignant soft tissue sarcoma* of 1 of the following cellular types:

  • Adipocytic (e.g., liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, not otherwise specified)
  • Fibroblastic (e.g., adult fibrosarcoma, myxofibrosarcoma, or sclerosing epithelioid fibrosarcoma)
  • So-called fibrohistiocytic (e.g., pleomorphic malignant fibrous histiocytoma [MFH], giant cell MFH, or inflammatory MFH)
  • Leiomyosarcoma
  • Malignant glomus tumors
  • Skeletal muscle (e.g., rhabdomyosarcoma, alveolar, or pleomorphic)
  • Vascular (e.g., epithelioid hemangioendothelioma or angiosarcoma)
  • Uncertain differentiation (e.g., synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor [PEComa], or intimal sarcoma)
  • Malignant peripheral nerve sheath tumors
  • Malignant solitary fibrous tumors
  • Undifferentiated soft tissue sarcomas not otherwise specified
  • Other types of sarcoma if approved by the study coordinator NOTE: *Includes malignant tumors of non-organ origin and skin and uterine leiomyosarcoma

• The following tumor types are excluded:

  • Embryonal rhabdomyosarcoma
  • Chondrosarcoma
  • Osteosarcoma
  • Ewing tumors/primitive neuroectodermal tumor (PNET)
  • Gastrointestinal stromal tumors
  • Dermatofibrosarcoma protuberans
  • Inflammatory myofibroblastic sarcoma
  • Neuroblastoma
  • Malignant mesothelioma
  • Mixed mesodermal tumors of the uterus
• Relapsed, refractory, and/or metastatic disease incurable by surgery or radiotherapy
• Measurable disease
• Must have formalin fixed paraffin-embedded tumor blocks and representative hematoxylin/eosin slides available for histological central review
• No symptomatic or known CNS metastases

PATIENT CHARACTERISTICS:

• At least 60 years of age OR ≥ 18 years of age if patient is not suitable for intensive combination chemotherapy treatments
• WHO performance status 0-1
• Absolute neutrophil count > 2,000/mm³
• Platelet count > 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine clearance ≥ 60 mL/min

• No serious cardiac illness within the past 6 months, including, but not limited to the following:

  • History of documented congestive heart failure
  • High-risk uncontrolled arrhythmias
  • Angina pectoris requiring antianginal medication
  • Clinically significant valvular heart disease
  • Evidence of transmural infarction on ECG
  • Poorly-controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
• Normal 12-lead ECG
• LVEF normal by MUGA or echocardiogram
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No other serious and/or unstable medical condition, illness, or lab abnormality that would preclude study participation
• No psychiatric illness or familial, social, or geographical condition that would preclude study compliance
• No active uncontrolled infection
• No known AIDS positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy regimen for advanced or metastatic disease (neoadjuvant and adjuvant therapy allowed)
• No concurrent sargramostim (GM-CSF) except in cases of febrile neutropenia

• No other concurrent anticancer therapy or investigational agents, including any of the following:

  • Chemotherapy
  • Biological response modifiers
  • Hormone therapy
  • Immunotherapy
• No other concurrent clinical treatment trial participation