Clinical trial NCT00112463: Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma
Official title: A Phase II Study of Single Agent Depsipeptide (FK228) in Metastatic or Unresectable Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-06-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Objective Tumor Response (Complete and Partial)
timeFrame: While on treatment - max of 16 months
measure: Time to Progression
timeFrame: Until disease progression - max of 48 months
measure: Toxicity as Assessed Using the Expanded Common Toxicity Criteria Version 3
timeFrame: During treatment (max of 16 months) and for 1 month following treatment
Secondary outcomes:
measure: Survival
timeFrame: Max of 98 months
Other outcomes:
Locations:
Study officials:
affiliation: Wake Forest University Health Sciences
name: Paul Savage
role: PRINCIPAL_INVESTIGATOR
References: