Intervention: Romidepsin
Trial phase: Phase 2
ATC code: L01XH02
SMILES: C/C=C1\NC(=O)[C@H]2CSSCC/C=C/[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@H](C(C)C)NC1=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 38
Group description: Patients receive depsipeptide (romidepsin) intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 6 additional courses beyond documentation of CR.
Eligibility criteria:
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) â¥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) â¤ 2.5 times upper limit of normal (ULN)
Bilirubin normal
Creatinine < 1.5 times ULN
Creatinine clearance ≥ 60 mL/min
QTc ≤ 480 msec

Exclusion Criteria:

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