A Phase 1, Open-label, Non-randomized, Dose-escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-102 in Combination With CPT-11 and Bevacizumab in Patients With Advanced Gastrointestinal Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 4
- 主要终点
- Determine maximum tolerated dose
研究概览
简要总结
The purpose of this study is to investigate the safety and determine the maximum tolerated dose of TAS-102 administered in combination with CPT-11 in patients with advanced gastrointestinal tumors.
详细描述
This is an open-label, non-randomized, dose-escalation, Phase 1 study of TAS-102 administered in combination with CPT-11. The study will be conducted in 2 parts: a Dose Escalation Phase (Part 1) to determine the maximum tolerated dose and an Expansion Phase (Part 2) to further evaluate the safety, pharmacokinetics, and preliminary efficacy of the maximum tolerated dose. Patients will be assigned to sequential dose-level cohorts with each cohort corresponding to a pre-specified dose of TAS-102 and CPT-11 combination. Escalation to the subsequent dose level will occur only after the previous dose level is determined to be safe.
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
- •Has provided written informed consent
- •Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
- •ECOG performance status of 0 or 1
- •Is able to take medications orally
- •Has adequate organ function (bone marrow, kidney and liver)
- •Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.
排除标准
- •Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
- •Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
- •Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies
- •Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
- •Is a pregnant or lactating female
- •Has had either partial or total gastrectomy
研究组 & 干预措施
TAS-102 and CPT-11 with or without Bevacizumab
干预措施: TAS-102 (Drug)
TAS-102 and CPT-11 with or without Bevacizumab
干预措施: CPT-11 (Drug)
TAS-102 and CPT-11 with or without Bevacizumab
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Determine maximum tolerated dose
时间窗: Through Cycle 1 and Cycle 2 (ie, 4 weeks)
The maximum tolerated dose is defined as the highest dose level at which less than 33% of the evaluable patients treated experience a dose-limiting toxicity during Cycle 1 or Cycle 2 (ie, during the first 4 weeks) of study drug administration.
Safety monitoring including adverse events, vital signs, and laboratory assessments
时间窗: Safety is assessed through 30 days following last administration of study medication or until initiation of new anticancer treatment.
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
次要结局
- Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites.(Blood samples will be collected in Cycle 1 at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24 and 48 hours post AM dose of TAS-102 in combination with CPT-11.)
- Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab.(After every 4 cycles (i.e., every 8 weeks))
- Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).(Through 30 days following last administration of study medication or until initiation of new anticancer treatment)