A Phase II Study of Single Agent Depsipeptide (FK228) in Metastatic or Unresectable Soft Tissue Sarcomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 主要终点
- Objective Tumor Response (Complete and Partial)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: romidepsin (Drug)
结局指标
主要结局
Objective Tumor Response (Complete and Partial)
时间窗: While on treatment - max of 16 months
Objective tumor response was evaluated using the criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee (JNCI 92(3):205-216,2000). Changes in only the largest diameter (unidimensional measurement) of the target lesions are used. A sum of the longest diameter (LD) for all target lesions was calculated and reported as the baseline sum LD. The baseline sum LD was used as reference by which to characterize the objective tumor response. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum LD; Overall Response (OR) = CR + PR
Time to Progression
时间窗: Until disease progression - max of 48 months
Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or a measurable increase in a non-target lesion, or the appearance of new lesions. Time to progression is the number of months from first treatment until the date of progression.
Toxicity as Assessed Using the Expanded Common Toxicity Criteria Version 3
时间窗: During treatment (max of 16 months) and for 1 month following treatment
The outcome reported here is the number (%) of participants who experienced grade 3 or greater toxicity while on study. A summary of the individual toxicities can be found in the AE/SAE results.
次要结局
- Survival(Max of 98 months)