NCT00537121已完成1 期
Phase I Study of Vorinostat [Suberoylanilide Hydroxamic Acid (VORINOSTAT)] With Irinotecan, 5-Fluorouracil (5-FU) and Leucovorin (FOLFIRI) for Advanced Upper Gastrointestinal Cancers
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) of vorinostat (SAHA) when administered continuously and intermittently with standard doses of irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI)
研究概览
简要总结
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with irinotecan, fluorouracil, and leucovorin in treating patients with advanced upper gastrointestinal cancer.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) of vorinostat (SAHA) when administered continuously with standard doses of irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with advanced upper gastrointestinal cancer.
- Determine the MTD and RPTD of SAHA when administered intermittently with standard doses of FOLFIRI in these patients.
Secondary
- Describe the toxicity of the SAHA and FOLFIRI combination.
- Explore the effects of SAHA and FOLFIRI combination on TGF-β expression.
- Explore the alteration of survivin expression by the SAHA and FOLFIRI combination.
- Describe the effect of FOLFIRI on the pharmacokinetics of SAHA.
- Describe the effect of SAHA on the pharmacokinetics of irinotecan.
- Describe the response rate, progression-free survival, and overall survival of patients treated with this regimen.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed upper gastrointestinal tract cancer, including any of the following:
- •Esophageal cancer (adenocarcinoma or squamous cell carcinoma)
- •Gastric cancer (adenocarcinoma or squamous cell carcinoma)
- •Hepatocellular carcinoma
- •Locally advanced, inoperable disease or metastatic disease
- •No uncontrolled brain metastases
- •PATIENT CHARACTERISTICS:
- •ECOG performance status (PS) 0-1 (Karnofsky PS ≥ 70%)
- •Life expectancy > 12 weeks
- •Platelet count ≥ 100,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcL
- •Leukocytes ≥ 3,000/mcL
- •Total bilirubin ≤ 1.5 mg/dL
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to understand and willing to sign a written informed consent document
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in the study
- •No uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Uncontrolled hypertension
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •No coagulopathy or bleeding disorder
- •No known UGT1A1 polymorphism
- •PRIOR CONCURRENT THERAPY:
- •No more than 1 prior chemotherapy for metastatic disease
- •No prior histone deacetylase inhibitors
- •No concurrent prophylactic hematologic growth factors
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent valproic acid
- •No other concurrent investigational therapy
- •Concurrent therapeutic anticoagulation therapy is allowed
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose (MTD) of vorinostat (SAHA) when administered continuously and intermittently with standard doses of irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI)
时间窗: 4 weeks
Recommended phase II dose (RPTD) of SAHA when administered continuously and intermittently with standard doses of FOLFIRI
时间窗: 4 weeks
次要结局
- Response rate(Every 6 months)
- Progression-free survival(Every 6 months)
- Overall survival(Every 3 months for 5 years)
- Toxicity of the SAHA and FOLFIRI combination(Baseline and after 2 weeks of Treatment)
- Effects of SAHA and FOLFIRI combination on TGF-β signaling and survivin expression(Every 6 months)
研究者
研究点 (2)
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