This is a Phase 1 open-label study to study the safety and activity of aldoxorubicin with ifosfamide/mesna in subjects with metastatic, advanced, unresectable soft tissue sarcoma.

Inclusion Criteria:

1. Age between 15-80 years, male or female.
2. 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.
3. Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma (including rhabdomyosarcoma, Ewing's sarcoma and mixed mesodermal sarcoma), chondrosarcoma or osteosarcoma of intermediate or high grade and gastrointestinal stromal tumors (GIST) (only in subjects that have progressed after receiving treatment with imatinib and sunitinib).
4. Capable of providing informed consent and complying with trial procedures.
5. ECOG performance status 0-2.
6. Life expectancy >12 weeks.
7. Measurable tumor lesions according to RECIST 1.1 criteria.
8. Women must not be able to become pregnant (eg 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.)
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and for 6 months after the final dose of study treatment.
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
11. Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria:

1. Prior chemotherapy unless for adjuvant or neoadjuvant therapy with no tumor recurrence for at least 12 months.
2. Prior exposure to >3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
3. Palliative surgery and/or radiation treatment less than 30 days prior to enrollment.
4. Exposure to any investigational agent within 30 days of enrollment.
5. Current Stage 1 or 2 soft tissue sarcomas.
6. Current evidence/diagnosis of alveolar soft part sarcoma, dermatofibrosarcoma, Kaposi's sarcoma, clear cell sarcomas and unresectable low grade liposarcomas.
7. Central nervous system metastasis if symptomatic.
8. 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.
9. 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, albumin <2 gm/dL, coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) >1.5 × ULN.
10. Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.