Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma

Inclusion Criteria:

* Age between 15-80 years (US only), and 18-80 (rest of world (ROW)), male or female.
* Adjuvant or neoadjuvant chemotherapy (including doxorubicin) allowed if no tumor recurrence for at least 12 months since the last measurement, beginning or end of last chemotherapy.
* Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma of intermediate or high grade.
* Capable of providing informed consent and complying with trial procedures.
* ECOG performance status 0-2.
* Life expectancy \> 12 weeks.
* Measurable tumor lesions according to RECIST 1.1 criteria.
* Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
* Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
* Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria:

* Prior chemotherapy unless for adjuvant or neoadjuvant therapy with no tumor recurrence for at least 12 months.
* Prior exposure to \> 3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
* Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
* Exposure to any investigational agent within 30 days of Randomization.
* Current Stage 1 or 2 soft tissue sarcomas.
* Current evidence/diagnosis of alveolar soft part sarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma, Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, clear cell sarcomas and unresectable low grade liposarcomas.
* Central nervous system metastasis
* History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for \> 5 years.
* Laboratory values: Screening serum creatinine \> 1.5x upper limit of normal (ULN), alanine aminotransferase (ALT) \> 3 × ULN or \>5 × ULN if liver metastases are present, total bilirubin \> 3 × ULN, absolute neutrophil count \< 1,500/mm3, platelet concentration \< 100,000/mm3, hematocrit level \< 25% for females or \< 27% for males, or coagulation tests (prothrombin time \[PT\], partial thromboplastin time \[PTT\], International Normalized Ratio \[INR\]) \> 1.5 × ULN, albumin \< 2.0 g/dL.
* Clinically evident congestive heart failure \> class II of the New York Heart Association (NYHA) guidelines.
* Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
* Baseline QTc \> 470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.
* History or signs of active coronary artery disease with or without angina pectoris.
* Serious myocardial dysfunction defined as scintigraphically (e.g. MUGA, myocardial scintigram) or ultrasound determined absolute left ventricular ejection fraction (LVEF) \< 45% of predicted.
* History of HIV infection.
* Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
* Major surgery within 3 weeks prior to Randomization.
* Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
* Any condition that is unstable and could jeopardize the subject's participation in the study.