A Phase 1 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Gemcitabine in Patients With Epithelial Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximally tolerated dose of a combination of SAHA and gemcitabine determined by dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously
研究概览
简要总结
This phase I trial is studying the side effects and best dose of vorinostat and gemcitabine in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as vorinostat and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity, maximum tolerated dose, and pharmacokinetics of vorinostat (SAHA) and gemcitabine in patients with metastatic or unresectable epithelial solid tumors.
SECONDARY OBJECTIVES:
II. Determine tumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation, open-label 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
- •ECOG 0-2 OR Karnofsky 60-100%
- •AST and ALT =< 2.5 times ULN
- •Bilirubin =< 1.5 times upper limit of normal (ULN)
- •Platelet count >= 100,000/mm3
- •Absolute neutrophil count >= 1,500/mm3
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Any number and type of prior chemotherapies are allowed including prior use of gemcitabine chemotherapy. A washout phase of at least 2 weeks since use of prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C, is required.
- •Patients must have histologically confirmed epithelial malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients must have at least one measurable lesion as per the RECIST Criteria that can be accurately measured in at least one dimension, with minimum lesion size equal to or more than twice the slice thickness of the imaging study used.
排除标准
- •No symptomatic congestive heart failure
- •No cardiac arrhythmia
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No history of allergy, significant side effects, or poor tolerance to gemcitabine
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA)
- •At least 2 weeks since prior radiotherapy
- •Recovered from prior therapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other uncontrolled illness
- •More than 2 weeks since prior valproic acid
- •No other concurrent investigational drugs
- •No other concurrent anticancer therapy
- •Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
研究组 & 干预措施
Arm I
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 patients are treated at the MTD
干预措施: vorinostat (Drug)
Arm I
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 patients are treated at the MTD
干预措施: gemcitabine hydrochloride (Drug)
结局指标
主要结局
Maximally tolerated dose of a combination of SAHA and gemcitabine determined by dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously
时间窗: 21 days
Pharmacokinetics of SAHA
时间窗: -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours after day 1 dose; -0.5 hours day 2; and -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours day 3
次要结局
- Best overall response (complete + partial response rate) as measured radiologically by RECIST(Up to 6 years)