Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
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 paclitaxel and carboplatin in treating patients with advanced or refractory solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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 paclitaxel and carboplatin may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Determine the recommended phase II dose of vorinostat (SAHA) when administered with paclitaxel and carboplatin in patients with advanced or refractory solid tumors.
SECONDARY OBJECTIVES:
I. Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in these patients.
II. Assess, preliminarily, evidence of antitumor activity of this regimen 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 confirmed solid tumor
- •No untreated brain metastases
- •Patients with stable brain disease (no concurrent corticosteroids) ≥ 4 weeks after completion of appropriate therapy are eligible
- •ECOG performance status ≤ 2 OR Karnofsky performance status 60-100%
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin normal
- •AST/ALT ≤ 2.5 times upper limit of normal
- •Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation
- •No peripheral neuropathy > grade 1
- •No history of allergic reactions to paclitaxel
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
- •No inability to take oral medications on a continuous basis
- •No psychiatric illness or social situation that would limit compliance with this study
- •No ongoing or active infection
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No other uncontrolled illness
- •No more than 2 prior chemotherapy regimens for advanced/metastatic disease
- •Adjuvant chemotherapy administered ≥ 2 years prior to study entry is not considered a prior chemotherapy regimen for purposes of this study
- •No prior therapy with paclitaxel
- •No chemotherapy or radiotherapy within the past 3 weeks (6 weeks for nitrosoureas or mitomycin C) and recovered
- •At least 4 weeks since prior valproic acid
- •No other concurrent anticancer therapies or agents
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent oral contraceptives
- •No concurrent prophylactic growth factors
排除标准
- 未提供
研究组 & 干预措施
Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
干预措施: vorinostat (Drug)
Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
干预措施: paclitaxel (Drug)
Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
干预措施: carboplatin (Drug)
Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
干预措施: laboratory biomarker analysis (Other)
Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
时间窗: 21 days
次要结局
- Toxicity graded using the CTC version 2.0(Up to 1 month after completion of study treatment)
- Overall survival(Up to 1 month after completion of study treatment)
- Time to failure(Up to 1 month after completion of study treatment)
- Response defined using the RECIST criteria(Up to 1 month after completion of study treatment)