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A Phase II Study of Single Agent Depsipeptide (FK228) in Metastatic or Unresectable Soft Tissue Sarcomas

Phase 2
18 Years
Open (Enrolling)
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

Thank you

Trial Information

A Phase II Study of Single Agent Depsipeptide (FK228) in Metastatic or Unresectable Soft Tissue Sarcomas


I. To estimate the response rates of metastatic or unresectable soft tissue sarcomas to
single-agent depsipeptide.

II. To estimate the time to progression of metastatic or unresectable soft tissue sarcomas
to single-agent depsipeptide.

III. To evaluate the scope and extent of acute toxicities associated with single-agent
depsipeptide when given to patients with soft tissue sarcomas.

OUTLINE: This is a multicenter study.

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.

After completion of study treatment, patients are followed up every 2 months.

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

- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective tumor response (complete and partial)

Outcome Description:

Estimated as the proportion of partial and complete responders.

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Paul Savage

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wake Forest University


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

Related Keywords:

  • 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
  • Histiocytoma
  • Chondrosarcoma
  • Fibrosarcoma
  • Hemangiopericytoma
  • Hemangiosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Mesenchymoma
  • Osteosarcoma
  • Rhabdomyosarcoma
  • Sarcoma, Synovial
  • Sarcoma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Histiocytoma, Benign Fibrous
  • Sarcoma, Alveolar Soft Part
  • Neurofibrosarcoma
  • Neurilemmoma
  • Gastrointestinal Stromal Tumors
  • Histiocytoma, Malignant Fibrous
  • Liver Neoplasms
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral



Memorial Medical CenterSpringfield, Illinois  62781
Southeastern Medical Oncology CenterGoldsboro, North Carolina  27534
Wellmont Holston Valley Hospital and Medical CenterKingsport, Tennessee  37662
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Bay Area Tumor Institution CCOPOakland, California  94609
Greenville CCOPGreenville, South Carolina  29615
Upstate Carolina CCOPSpartanburg, South Carolina  29303
Danville Hematology OncologyDanville, Virginia  24541
Carolina Health CareFlorence, South Carolina  29501
Central Illinois CCOPDecatur, Illinois  62526
Southeast Cancer Control Consortium Inc CCOPWinston Salem, North Carolina  27104