An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7050 in Combination With Sorafenib Versus Sorafenib Alone as First Line Therapy in Patients With Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 102
- 主要终点
- Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
研究概览
简要总结
The purpose of this study is to determine whether patients with hepatocellular carcinoma who receive either E7050 administered with Sorafenib or Sorafenib alone experience greater benefit (cancer responds to treatment) when E7050 is administered with Sorafenib.
详细描述
This open-label, multicenter, randomized study will consist of a Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with sorafenib; and a Phase II portion: a randomized 2-arm period. Approximately 95 patients with hepatocellular carcinoma will be enrolled in the study (10-15 patients in the Phase Ib portion and 80 patients in the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II portion of the study. In both Phase Ib and phase II, Patients will receive study treatment (E7050 plus sorafenib or sorafenib alone) until the occurrence of progressive disease (PD)for approximately six 28-day cycles (24 weeks). After 6 cycles. ath the discretion of the Investigator and in consultation with the Medical Monitor, patients who are experiencing clinical benefit may continue E7050, with or without sorafenib (Arm 1), or may continue sorafenib alone (Arm 2), depending on the original randomization treatment arm, for as long as clinical benefit is sustained and the treatment is well tolerated. Patients will be followed until death following completion of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
Phase Ib: Cohort 1,2, and 3
Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib
干预措施: Sorafenib (Drug)
Phase II: Arm 1; E7050 + Sorafenib
Phase II: Arm 1; E7050 + 400 mg Sorafenib Arm 2; 400 mg Sorafenib
干预措施: Sorafenib (Drug)
结局指标
主要结局
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
时间窗: Cycle 1 Day 28: 0-24 hours post-dose (Cycle length is 28 days)
Phase 2: Number of Participants With Worst Shifts Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Number of participants with worst shifts post baseline in ECOG-PS levels were reported. ECOG has 6 levels (0-5). Level 0 is the best status (fully active, able to carry on all pre-disease performance without restriction); Level 1 is mildly restricted (Restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work); Level 2 is more restricted (Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours); Level 3 is restricted (Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours); Level 4 is highly restricted (completely disabled; cannot carry on any selfcare; totally confined to bed or chair); and Level 5 is death (dead).
Phase 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)
时间窗: Cycle 1 (Cycle length is 28 days)
DLTs were defined as clinically significant adverse events (AEs) (non-hematological, hematological and other events) occurring less than or equal to (\<=) 28 days after commencing study treatment and considered to be at least possibly or probably related to study drug by the Investigator. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
时间窗: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 2: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure Including Systolic and Diastolic Blood Pressures
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7
时间窗: Day -7: 0-72 hours post-dose
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
时间窗: Cycle 1 Day 28: 0-24 hours post-dose
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
时间窗: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
时间窗: Cycle 1 Day 28: 0-24 hours post-dose
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day -7
时间窗: Day -7: 0-72 hours post-dose
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
时间窗: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 2: Number of Participants With Adverse Events Related to Vital Signs
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Number of participants are reported with AEs related to Vital signs including body temperature, respiratory rate, heart rate, height, and weight.
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With AEs by Severity Grades
时间窗: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
AE severity was graded using CTCAE version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Higher grade indicates more severe condition.
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7
时间窗: Day -7: 0-72 hours post-dose
Phase 1b: t1/2: Terminal Elimination Half-life for Golvatinib When Administered in Combination With Sorafenib at Day -7
时间窗: Day -7: 0-72 hours post-dose
次要结局
- Phase 2: Overall Survival (OS)(From the date of randomization until the date of death (Up to approximately 3 years 11 months))
- Phase 2: Progression Free Survival (PFS)(From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 11 months))
- Phase 2: Percentage of Participants With PFS at Week 12(At 12 weeks)
- Phase 2: Time to Progression (TTP)(From the date of randomization until the date of PD (up to approximately 3 years 11 months))
- Phase 2: Percentage of Participants With Overall Response(From the date of randomization until disease progression or death (Up to approximately 3 years 11 months))