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