Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112463
First received: June 2, 2005
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: romidepsin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Single Agent Depsipeptide (FK228) in Metastatic or Unresectable Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response (complete and partial) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated as the proportion of partial and complete responders.

  • Toxicity as assessed using the Expanded Common Toxicity Criteria version 3 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: From first treatment until the date of progression, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: From first treatment until death or the last date of contact, assessed up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: January 2004
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (single-agent depsipeptide)
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.
Drug: romidepsin
Other Names:
  • FK228
  • FR901228
  • Istodax

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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) ⥠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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112463

Locations
United States, California
Bay Area Tumor Institute
Oakland, California, United States, 94609
Bay Area Tumor Institution CCOP
Oakland, California, United States, 94609
United States, Illinois
Central Illinois CCOP
Decatur, Illinois, United States, 62526
Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, North Carolina
Southeastern Medical Oncology Center
Goldsboro, North Carolina, United States, 27534
Southeast Cancer Control Consortium Inc CCOP
Winston Salem, North Carolina, United States, 27104
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, South Carolina
Carolina Health Care
Florence, South Carolina, United States, 29503-1905
Greenville CCOP
Greenville, South Carolina, United States, 29615
Upstate Carolina CCOP
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, United States, 37660
United States, Virginia
Danville Hematology Oncology
Danville, Virginia, United States, 24541
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Savage Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112463     History of Changes
Obsolete Identifiers: NCT01645683
Other Study ID Numbers: NCI-2012-01037, NCI-2012-01037, CDR0000433042, CCCWFU 71103, 6319, U10CA081851
Study First Received: June 2, 2005
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Neoplasms, Muscle Tissue

ClinicalTrials.gov processed this record on April 16, 2014