Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma
Condition: Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma
MeSH terms: Sarcoma; Osteosarcoma; Gastrointestinal Stromal Tumors; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Leiomyosarcoma; Liposarcoma; Chondrosarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Synovial; Hemangiosarcoma; Fibrosarcoma; Sarcoma, Alveolar Soft Part; Histiocytoma; Hemangiopericytoma; Solitary Fibrous Tumors; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous; Neurofibrosarcoma; Mesenchymoma; Recurrence
Intervention: romidepsin
Intervention description: DEP is administered at a dose of 13 mg/m2 as a 4-hour intravenous infusion in the outpatient setting.
Intervention MeSH terms: Romidepsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well depsipeptide (romidepsin) works in treating patients
      with metastatic or unresectable soft tissue sarcoma. Drugs used in chemotherapy, such as
      depsipeptide, work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing.
    

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