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

Gastrointestinal Stromal Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00112463
• Other study ID #: NCI-2012-01037
• Secondary ID: NCI-2012-01037CD
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 2, 2005
• Last updated: November 3, 2016
• Start date: January 2004

Study information

• Verified date: November 2016
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01645683

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• 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
• Chondrosarcoma
• Fibrosarcoma
• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors
• Hemangiopericytoma
• Histiocytoma
• Histiocytoma, Malignant Fibrous
• Leiomyosarcoma
• Liposarcoma
• Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neuroectodermal Tumors, Primitive, Peripheral
• Osteosarcoma
• Recurrent Adult Soft Tissue Sarcoma
• Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Alveolar Soft Part
• Sarcoma, Ewing
• Sarcoma, Synovial
• Stage III Adult Soft Tissue Sarcoma
• Stage IV Adult Soft Tissue Sarcoma

Intervention

Drug:
• romidepsin

Locations

Country	Name	City	State
United States	Danville Hematology Oncology	Danville	Virginia
United States	Central Illinois CCOP	Decatur	Illinois
United States	Carolina Health Care	Florence	South Carolina
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Greenville Health System Cancer Institute/Eastside	Greenville	South Carolina
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Bay Area Tumor Institute CCOP	Oakland	California
United States	Bay Area Tumor Institution CCOP	Oakland	California
United States	Upstate Carolina CCOP	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Southeast Cancer Control Consortium Inc CCOP	Winston Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response (complete and partial)	Estimated as the proportion of partial and complete responders.	Up to 5 years	No
Primary	Toxicity as assessed using the Expanded Common Toxicity Criteria version 3		Up to 5 years	Yes
Primary	Time to progression		From first treatment until the date of progression, assessed up to 5 years	No
Primary	Survival		From first treatment until death or the last date of contact, assessed up to 5 years	Yes