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

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