A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
研究概览
简要总结
This phase I trial is studying the side effects and best dose of vorinostat when given together with alvocidib in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as vorinostat and alvocidib, 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. Giving vorinostat together with alvocidib may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.
II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.
III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).
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 confirmed solid tumor
- •Metastatic or unresectable disease
- •Standard curative or palliative measures do not exist or are no longer effective
- •No hematologic malignancies
- •No known brain metastases
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 1.5 mg/dL
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
- •No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situations that would preclude study compliance
- •Recovered from prior therapy
- •At least 2 weeks since prior histone acetylase inhibitors, including valproic acid
- •At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •At least 2 weeks since prior investigational therapy
- •At least 2 weeks since prior radiotherapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent commonly used vitamins, antioxidants, or herbal preparations and supplements
- •A single tablet multivitamin is allowed
- •No other concurrent anticancer agents or therapies for this mailgnancy
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: alvocidib (Drug)
Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
时间窗: Course 1
Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course. Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
次要结局
- Clinical pharmacokinetics of vorinostat (SAHA)(Week 1 of course 1)
- Therapeutic activity of SAHA and flavopiridol(Not Provided)
- Expression of p21, p53, and apoptotic markers relative to treatment response(Baseline to 2 weeks after completion of study treatment)