An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7050 in Combination With Cisplatin and Capecitabine Versus Cisplatin and Capecitabine Alone in Patients With Advanced or Metastatic Solid Tumors and Previously Untreated Gastric Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Eisai Inc.
- 入组人数
- 7
- 试验地点
- 19
- 主要终点
- Time to Maximum Concentration (Tmax) of Golvatinib
研究概览
简要总结
The purpose of this study is to determine the following: 1. Find the maximum tolerated dose of E7050 when given in combination with cisplatin and capecitabine in patients with advance or metastatic solid tumors, and 2) Whether E7050 in combination with cisplatin and capecitabine is more effective in patients with previously untreated gastric cancer versus cisplatin and capecitabine alone.
详细描述
This open-label, multicenter, randomized study will consist of 2 phases:
Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with fixed doses of Cisplatin and Capecitabine. This phase will enroll approximately 10 to 15 patients.
- Phase II: a randomized 2-arm design which will enroll 80 patients.
In the phase II portion, Patients will receive study treatment , E7050 in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone) for approximately six 21-day cycles (18 weeks). Beyond 18 weeks, patients who are experiencing clinical benefit may continue E7050, with or without Capecitabine (Arm 1), or may continue Capecitabine alone (Arm 2), depending on the original randomization treatment arm. Patients will continue treatment for as long as clinical benefit is sustained and the treatment is well tolerated, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first. Patients will participate in either phase Ib or phase II.
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 and 2 and 3
Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine
Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: E7050 (Drug)
Phase Ib: Cohort 1 and 2 and 3
Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine
Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: cisplatin (Drug)
Phase Ib: Cohort 1 and 2 and 3
Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine
Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: capecitabine (Drug)
Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: E7050 (Drug)
Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: cisplatin (Drug)
Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
干预措施: capecitabine (Drug)
结局指标
主要结局
Time to Maximum Concentration (Tmax) of Golvatinib
时间窗: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib
时间窗: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
On days when pharmacokinetic (PK) samples were to be drawn, a predose blood sample was obtained prior to administration of golvatinib and capecitabine. After administration of study drugs, a second postdose blood sample was taken. The amount of golvatinib in the participant's blood was analyzed and the AUC was calculated. The AUC reflects the actual body exposure to drug after administration of a dose of the drug and is dependent on the rate of elimination of the drug from the body and the dose administered. Predose samples that were below the limit of quantitation (BLQ) or missing were assigned a numerical value of zero for the calculation of AUC. Any other BLQ concentrations were assigned a value of zero. Results were expressed in nanograms·hour/milliter (ng·h/mL).
Maximum Concentration (Cmax) of Golvatinib
时间窗: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
Blood samples were drawn to analyze the amount of golvatinib in the participant's serum. Maximum concentration refers to the maximum (or peak) serum concentration of study drug in the participant's system after administration of the study drug and prior to the administration of a second dose of the study drug. Results were expressed in nanograms/milliliter (ng/mL).
Number of Participants With a Treatment-Emergent Adverse Event (TEAE)
时间窗: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.
Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious AEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an adverse event (AE) that had an onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to 30 days after the date of last study treatment.
次要结局
- Overall Response Rate (ORR)(Until disease progression or death for 3 years)
- Time to Progression (TTP)(Until disease progression or death for 3 years)