A Phase I, Open-Label Study to Investigate the Safety and Tolerability of AZD6244 (Selumetinib) When Given as a Monotherapy in Japanese Patients With Advanced Solid Malignancies, and When Given in Combination With Docetaxel as 2nd Line Therapy in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
研究概览
简要总结
The objective of this study will be to investigate the safety and tolerability of AZD6244 given monotherapy or in combination with docetaxel as 2nd line therapy in Japanese patients with Advanced Solid Malignancies or Locally Advanced or Metastatic Non-Small Cell Lung Cancer. In addition, the pharmacokinetic profile of AZD6244 will be investigated. Following the combination regimen dose escalation phase (Part A) of the study additional patients may be enrolled to a dose expansion phase (Part B) to refine further the safety, tolerability, pharmacokinetics and biological activity of the combination in this patient population.
详细描述
The objective of the combination therapy part of this study will be to investigate the safety and tolerability of AZD6244 given in combination with docetaxel as 2nd line therapy in Japanese patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV). In addition, the pharmacokinetic profile of AZD6244 and docetaxel will be investigated.
The objective of the monotherapy part of this study will be to investigate the safety and tolerability of AZD6244 given as a monotherapy in Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile of monotherapy AZD6244 will be investigated.
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
- 20 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with lung cancer who have not responded to prior therapy or have become worse.
- •Patients who have overall good general conditions.
- •Patients who have at least one lesion that can be accurately assessed by imaging.
- •Patients who have appropriate renal conditions confirmed by test results for taking part in the study.
- •Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status.
排除标准
- •Patients with brain metastases or spinal cord compression.
- •Patients with significant abnormal ECG findings.
- •Patients with evidence of severe or uncontrolled systemic disease.
- •The main organ functional test values for bone marrow, kidney, and liver, etc., do not meet the standards.
- •Patients with known hypersensitivity to docetaxel or products containing polysorbate
- •Only for monotherapy cohort eligibility criteria Patients with advanced solid malignancies refractory to standard treatment or for which no standard therapy exists irrespective of the stage and previous treatment.
- •Patients with histologically or cytologically confirmed advanced solid malignancies.
研究组 & 干预措施
Selumetinib (AZD6244) 25 mg
monotherapy
干预措施: AZD6244 (Drug)
Selumetinib (AZD6244) 50 mg
monotherapy
干预措施: AZD6244 (Drug)
Selumetinib (AZD6244) 75 mg
monotherapy
干预措施: AZD6244 (Drug)
Selumetinib (AZD6244) 75 mg + Doce
Combination
干预措施: AZD6244 (Drug)
Selumetinib (AZD6244) 25 mg + Doce
combination
干预措施: AZD6244 (Drug)
结局指标
主要结局
Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
AUC(0-12) of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Cmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Cmax of Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
Tmax of Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
AUC(0-12) of Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dosey) of Selumetinib following single oral dose of Selumetinib
Cmax of N-desmethyl Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
Tmax of N-desmethyl Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
AUC(0-12) of N-desmethyl Selumetinib After Single Dose
时间窗: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib following single oral dose of Selumetinib
AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of Selumetinib during oral twice daily dose of Selumetinib
Tmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
时间窗: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
次要结局
- Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2(Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose)
- AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2(Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose)
- Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2(Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose)