A Multicenter, Phase 1/1b, Open Label Study Evaluating the Safety, Tolerability and Pharmacokinetics of Rilotumumab in Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Part1: Dose-limiting toxicities (DLT) for each dose level of rilotumumab tested
研究概览
简要总结
This is an open label phase 1/1b study of Rilotumumab in Japanese subjects with advanced solid tumors or metastatic gastric esphagogastric (GEJ) adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese subjects with pathologically confirmed unresectable locally advanced or metastatic carcinoma which is refractory to standard therapies or for which there is no standard therapy (Part 1 only)
- •Japanese subjects with pathologically confirmed MET-positive (fulfilling the MET IHC criteria as defined by validated IVD [in vitro diagnostic]) unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma (Part 2 only)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (0 or 1)
- •Availability of archival tumor tissue (Part 2 only)
- •Evaluable (measurable or non-measurable) disease by RECIST 1.1 criteria
- •Able to tolerate infusions and take oral medications (Part 2 only)
排除标准
- •Previous systemic therapy (including chemotherapy, biologic, immunotherapy, or investigational therapy) for locally advanced or metstatic gastric or GEJ adenocarcinoma (Part 2 only)
- •Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemotherapy to enrollment (Part 2 only)
- •Squamos cell history (Part 2 only)
- •Known HER2-overexpressing unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma (Part 2 only)
- •Resectable disease or suitable for definitive chemoradiation
- •Subjects who have persistent gastric outlet obstruction, complete dysphagia or are dependent upon jejunostomy for feeding (Part 2 only)
- •Known central nervous system metastases
研究组 & 干预措施
Rilotumumab Monotherapy
Cohort 1A: Rilotumumab 10 mg/kg IV Q2W Cohort 1B: Rilotumumab 20 mg/kg IV Q2W Cohort 1C (if needed): Rilotumumab 15 mg/kg IV Q2W
干预措施: Rilotumumab (Drug)
Rilotumumab plus CX
Cohort 2A: Rilotumumab 15 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W Cohort 2B (if needed): Rilotumumab 10 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W
干预措施: Rilotumumab (Drug)
结局指标
主要结局
Part1: Dose-limiting toxicities (DLT) for each dose level of rilotumumab tested
时间窗: 28 days
DLTs are defined as grade 3 or higher adverse events that are related to rilotumumab during the first cycle of therapy. This does not include specific toxicities (eg nausea and vomiting) that are common in cancer patients unless specific criteria are met.
Part 2: Dose-limiting toxicities (DLT) for each dose level of rilotumumab in combination with cisplatin and capecitabine (CX) chemotherapy tested
时间窗: 21 days
DLTs are defined as grade 3 or higher adverse events that are related to rilotumumab or the combination of rilotumumab and CX during the first cycle of therapy. This does not include specific toxicities (eg nausea and vomiting) that are common in cancer patients unless specific criteria are met.
次要结局
- Part 1: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies.(4 months average)
- Part 1: Pharmacokinetics parameters of rilotumumab monotherapy as measured by: Maximum concentration, time to achieve maximum concentration, observed minimum concentration, area under the concentration-time curve, terminal elimination half-life.(4 months average)
- Part 1: Evaluate efficacy based on the treatment effects of rilotumumab monotherapy as measured by the following: Objective Response Rate, duration of response, progression-free survival.(4 months average)
- Part 2: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies not defined as DLTs.(7 months average)
- Part 2: Pharmacokinetics parameters of rilotumumab in combination with cisplatin and capecitabine as measured by: Maximum concentration, observed minimum concentration, area under the concentration-time curve.(7 months average)
- Part 2: Evaluate efficacy based on the treatment effects of rilotumumab in combination with cisplatin and capecitabine as measured by the following: Objective Response Rate, duration of response, progression-free survival, overall survival.(7 months average)