A Phase I Dose Escalation Study of Nelfinavir Plus MLN9708 in Patients With Advanced Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of nelfinavir
研究概览
简要总结
This is an open label, dose escalation, phase I study of the combination of MLN9708 plus Nelfinavir.
详细描述
This is an open label, dose escalation, phase I study of the combination of MLN9708 MLN9708 plus Nelfinavir. It will use a 3+3 cohort design to determine the maximum tolerated dose of the combination, which will be defined as the highest dose cohort where < 1/6 patients develop a dose limiting toxicity. The maximum tolerated dose cohort will be expanded to have at least 6 patients with biopsiable tumors who undergo pretreatment and post treatment tumor biopsies for molecular pharmacodynamic markers.
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
Nelfinavir plus MLN9708
Both Nelfinavir and MLN9708 will be given orally (by mouth). MLN9708 will be given as 3 mg orally twice weekly. Study drugs will be administered on 21-day treatment cycles. All cycles are 21 days.
During the first cycle of MLN9708 only will initially be administered orally at a fixed dose of 3mg twice weekly for 2 weeks, on Mondays and Thursdays during this treatment cycle. During the third week there will be no study combination drug therapy(for Cycle 1 only). During Cycles 2 and 3, MLN9708 administered twice weekly on Mondays and Thursdays for the first 2 weeks of Cycles 2 and 3. Nelfinavir (escalating cohorts [1250mg, 1875mg, 2500mg, 3125mg]) will be administered orally twice daily in the dose cohorts listed.
干预措施: MLN9708 (Drug)
Nelfinavir plus MLN9708
Both Nelfinavir and MLN9708 will be given orally (by mouth). MLN9708 will be given as 3 mg orally twice weekly. Study drugs will be administered on 21-day treatment cycles. All cycles are 21 days.
During the first cycle of MLN9708 only will initially be administered orally at a fixed dose of 3mg twice weekly for 2 weeks, on Mondays and Thursdays during this treatment cycle. During the third week there will be no study combination drug therapy(for Cycle 1 only). During Cycles 2 and 3, MLN9708 administered twice weekly on Mondays and Thursdays for the first 2 weeks of Cycles 2 and 3. Nelfinavir (escalating cohorts [1250mg, 1875mg, 2500mg, 3125mg]) will be administered orally twice daily in the dose cohorts listed.
干预措施: Nelfinavir (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of nelfinavir
时间窗: Approximately 1 year to establish MTD
If 0/3 patients experience dose limiting toxicity, 3 patients will be treated at the next dose level. If dose limiting toxicity attributable to the study drug(s) is experienced in exactly 1/3 patients, 3 more patients (for a total of 6) will be treated at that dose level. If no additional dose limiting toxicity is observed at the expanded dose level (i.e. 1/6 with dose limiting toxicity), the dose will be escalated. Escalation will terminate as soon as two or more patients experience any dose limiting toxicity attributable to the study drug(s), at a given dose level. If 2 or more dose limiting toxicities are observed in any cohort, no further escalation will take place, and the Maximum Tolerated Dose will have been exceeded.
The toxicity of MLN9708 when combined with nelfinavir based on CTCAE grading criteria v. 4.0
时间窗: Approximately 18-24 months to observe toxicity
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI Revised Common Toxicity Criteria and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
次要结局
- The anti-tumor activity of the MLN9708/Nelfinavir(The study as a whole is estimated to be completed in 18-24 months.)
- Pharmacokinetics of both MLN9708 and nelfinavir based on parameters estimated using WinNonLin(The study as a whole is estimated to be completed in 18-24 months.)
- Pharmacodynamics of MLN9708 based on peripheral blood mononuclear cells (PBMCs)(The study as a whole is estimated to be completed in 18-24 months.)
- Pharmacodynamics of MLN9708 based on tumor tissue(The study as a whole is estimated to be completed in 18-24 months.)