A Phase I/II Study of Nelfinavir in Liposarcoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Dose Limiting Toxicity (DLT) (Phase I)
研究概览
简要总结
RATIONALE: Antiviral drugs, such as nelfinavir mesylate, may help prevent cancer cells from spreading.
PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir mesylate and to see how well it works in treating patients with recurrent, metastatic, or unresectable liposarcoma.
详细描述
OBJECTIVES:
I. To assess the toxicity and tolerance of nelfinavir in patients with liposarcoma.
II. To define the maximum tolerated dose (MTD) of nelfinavir when given daily as a single agent and to describe the toxicities at each does studied.
III. To evaluate the pharmacokinetics of nelfinavir. IV. To assess the response rate and progression free survival in patients with liposarcoma treated with nelfinavir.
V. To evaluate the expression and activity of certain proteins in the tumors of patients entered on this study, which may be important to the cytotoxicity of nelfinavir (SREBP-1, p21, NFkB (NFkappaB), caspase 3).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: nelfinavir mesylate (Drug)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: biopsy (Procedure)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: gene expression analysis (Genetic)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: western blotting (Genetic)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: reverse transcriptase-polymerase chain reaction (Genetic)
Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: immunoenzyme technique (Other)
结局指标
主要结局
Dose Limiting Toxicity (DLT) (Phase I)
时间窗: 4 weeks from start of treatment, up to 2 years
DLT is defined as any grade III toxicity not reversible to grade II or less within one week, or any grade IV toxicity. Hyperlipidemia, hyperglycemia, nausea, vomiting and diarrhea are not DLTs unless they are uncontrolled grade 3/4. Dose delays lasting more than 2 weeks due to toxicity are considered a DLT. Dose escalation schedule for nelfinavir: 1250 mg bid ; 1500 mg bid; 2125 mg bid; 3000 mg bid; 4250 mg bid ; 6000 mg bid ; 8500 mg bid ; 12000 mg bid
Maximum Tolerated Dose (MTD) (Phase I)
时间窗: 4 weeks from start of treatment, up to 2 years
The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. If PK analysis of 3 patients treated at 4250 mg bid and 3 patients at 3000 mg bid confirms that the first dose area under the curve and Cmax of nelfinavir does not increase appreciably at doses greater than 1875 mg BID then 3000 mg BID will be deemed the MTD.
Overall Response Rate (Phase II)
时间窗: After 3 cycles of treatment, up to 2 years.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
次要结局
未报告次要终点