A Phase 2 Study of Single Agent Depsipeptide (FK228) in Gastric and Esophageal Cancers
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Radiographic response rate (complete response & partial response)
研究概览
简要总结
This phase II trial is studying how well FR901228 works in treating patients with refractory stomach cancer or gastroesophageal junction. Drugs used in chemotherapy, such as FR901228, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. FR901228 may also stop the growth of tumor cells by blocking some of the enzymes needed for their growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine the radiographic response rate (complete response and partial response) in patients with refractory adenocarcinoma of the stomach or gastroesophageal junction treated with FR901228 (depsipeptide).
SECONDARY OBJECTIVES:
I. Determine the median time to progression and progression-free survival of patients treated with this drug.
II. Determine the grade 3 and 4 toxic effects of this drug in these patients.
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 adenocarcinoma of the stomach or gastroesophageal junction
- •Measurable disease
- •At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- •Refractory* to at least 1, but no more than 3, of the following first-line agents:
- •Fluoropyrimidine (e.g., capecitabine or fluorouracil)
- •Taxane (e.g., paclitaxel or docetaxel)
- •Platinum (e.g., carboplatin, cisplatin, or oxaliplatin)
- •No known active brain metastases
- •Treated brain metastases allowed provided metastases are stable off steroids for ≥ 30 days
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •At least 3 months
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
- •Creatinine clearance ≥ 50 mL/min
- •No congestive heart failure
- •No New York Heart Association class III or IV heart disease
- •No myocardial infarction within the past 6 months
- •No ventricular arrhythmias requiring medication
- •No angioplasty or vascular stenting within the past 3 months
- •No unstable angina
- •No left ventricular hypertrophy by EKG
- •No known history of serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- •QTc < 500 msec
- •LVEF > 40% by MUGA or echocardiogram
- •No other significant cardiac disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Potassium ≥ 4.0 mmol/L (stable level with no change in supplementation within the past 2 weeks)
- •Magnesium ≥ 2.0 mg/dL (stable level with no change in supplementation within the past 2 weeks)
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drug
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •Prior biological agents allowed
- •No concurrent prophylactic filgrastim (G-CSF)
- •No concurrent biologic therapy
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No other concurrent chemotherapy
- •More than 4 weeks since prior radiotherapy and recovered
- •No concurrent radiotherapy
- •Prior targeted agents allowed
- •No other prior or concurrent cytotoxic agents
- •No other concurrent investigational agents
- •No other concurrent anticancer therapy
- •No concurrent medications causing QTc prolongation
- 另有 3 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (romidepsin)
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: romidepsin (Drug)
Treatment (romidepsin)
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Radiographic response rate (complete response & partial response)
时间窗: Not Provided
次要结局
- Toxicity(Not Provided)
- Frequency of treatment related grade 1-4 toxicities and cardiac toxicities as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0(Up to 12 months)
- Correlation of changes in gene expression profile in dermal granulation tissue pre- and post-treatment with gene expression profile(Not Provided)
- Correlation of wound vascular scores pre- and post-treatment with gene/protein changes(Not Provided)
- Changes in gene expression profile(At pre- and post-treatment)
- Changes in levels of p21 and thymidine kinase expression, and tubulin acetylation using Western blotting(From baseline to 3 weeks)
- Changes in gene expression profile in dermal granulation tissue(From baseline to up to 3 weeks)
- Change in plasma and urine TGFB levels(At pre-and post-treatment)
- Progression-free survival (PFS) according to RECIST(Up to more than 6 months)