Inclusion Criteria:

- Histologically or cytologically confirmed soft tissue sarcoma (STS), including, but
not limited to, the following histologies:

- Gastrointestinal stromal tumors (GIST)

- Refractory to imatinib mesylate

- Desmoplastic small round cell tumors

- Clear cell sarcoma

- Extraskeletal osteosarcoma*

- Extraskeletal Ewing's sarcoma*

- Extraskeletal (myxoid) chondrosarcoma*

- Secondary STS (e.g., radiation-induced STS or neurofibrosarcoma due to
neurofibromatosis) allowed

- Metastatic or unresectable disease

- No standard curative therapy exists

- Patients with GIST must have received and progressed on imatinib mesylate

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- No known brain metastases

- Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2

- Performance status - Karnofsky 50-100%

- More than 3 months

- White blood cells (WBC) ⥠3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ⤠2.5 times
upper limit of normal (ULN)

- Bilirubin normal

- Creatinine < 1.5 times ULN

- Creatinine clearance ≥ 60 mL/min

- QTc ≤ 480 msec

- No cardiac abnormalities (e.g., congenital long QT syndrome)

- No myocardial infarction within the past year

- No history of coronary artery disease (e.g., angina Canadian Class II-IV or positive
stress imaging study)

- No cardiac ischemia (ST depression >2 mm) by electrocardiogram (ECG)

- No New York Heart Association Class II-IV congestive heart failure

- Ejection fraction > 50% by multi gated acquisition scan (MUGA) scan or echocardiogram

- No history of sustained ventricular tachycardia, ventricular fibrillation, Torsades
de Pointes, or cardiac arrest unless controlled by an automatic implantable
cardioverter defibrillator

- No hypertrophic or restrictive cardiomyopathy from prior treatment or other causes

- No significant left ventricular hypertrophy

- No uncontrolled hypertension (i.e., blood pressure ≥ 160/95 mm Hg)

- No cardiac arrhythmia requiring anti-arrhythmic medication

- Beta blocker or calcium channel blocker allowed

- Patients on digitalis that cannot be discontinued not allowed

- No Mobitz II second degree block without a pacemaker (first degree or Mobitz I second
degree block, bradyarrhythmias, or sick sinus syndrome require Holter monitoring and
evaluation by cardiology)

- No uncontrolled dysrhythmia

- No poorly controlled angina

- No other cardiac disease

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to FR901228

- No ongoing or active infection

- No iatrogenic immune deficiency or immune deficiency secondary to an underlying
disorder

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Potassium ≥ 4.0 mmol/L

- Magnesium ≥ 2.0 mg/dL

- No other uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

- No concurrent anticancer biologic agents

- No more than 1 prior chemotherapy regimen for sarcoma

- Adjuvant chemotherapy preceding disease relapse is considered 1 prior
chemotherapy regimen

- Patients with GIST may have received up to 3 prior chemotherapy regimens
comprising imatinib mesylate and/or sunitinib malate provided no other
chemotherapy agents were used

- No prior FR901228 (depsipeptide)

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No prior cumulative doxorubicin dose > 500 mg/m^2

- No other concurrent anticancer chemotherapy

- At least 4 weeks since prior radiotherapy

- No concurrent anticancer radiotherapy

- At least 4 weeks since prior surgery

- No prior organ transplantation

- Recovered from all prior therapy

- No concurrent medications that cause QTc prolongation

- No concurrent combination highly active anti-retroviral therapy for HIV-positive
patients

- No other concurrent drugs known to have histone deacetylase inhibitor activity (e.g.,
sodium valproate)

- No other concurrent investigational agents

- No other concurrent anticancer agents