TRUSTS: A Phase IIB/III Multicenter Study Comparing the Efficacy of TRabectedin Administered as a 3-Hour or 24-Hour Infusion to Doxorubicin in Patients With Advanced or Metastatic Untreated 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