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

Inclusion Criteria

• •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