Phase I/Ib Study of Crenolanib With Ramucirumab and Paclitaxel as Second Line Therapy for Advanced Esophagogastric Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- MTD of oral continuous dosing of crenolanib (3 different doses) plus ramucirumab/paclitaxel in patients defined as the highest dose level in which <2 of 6 patients develop a DLT. The DLT is based on the 1st cycle adverse events.
研究概览
简要总结
This is a single-arm phase I/Ib study of crenolanib combined with ramucirumab/paclitaxel as second line therapy for patients with advanced/metastatic adenocarcinoma of the esophagus, GEJ or stomach. Patients will be enrolled in two phases; dose escalation phase and dose expansion phase.
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
- •Pathologically confirmed adenocarcinoma of the esophagus, GEJ or stomach.
- •Stage IV disease or locally advanced/unresectable tumors
- •Prior progression on only 1 line of chemotherapy in the advanced/metastatic setting containing a fluoropyrimidine and/or platinum compound
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
排除标准
- •Prior treatment with a taxane is not permitted in the dose-expansion phase. Patients in the dose escalation component may have received a taxane in the peri-operative setting, provided they developed disease recurrence >6 months after the completion of this therapy
- •Known pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
- •Patients with any clinically apparent ascites or who have undergone a paracentesis within 7 days of enrollment
- •Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management
- •Active or clinically significant cardiac disease
- •Patients with arterial thrombotic events, such as cerebrovascular accident or myocardial infarction, within 6 months of enrollment
研究组 & 干预措施
Crenolanib combined with ramucirumab/paclitaxel
干预措施: Crenolanib (Drug)
Crenolanib combined with ramucirumab/paclitaxel
干预措施: Ramucirumab (Drug)
Crenolanib combined with ramucirumab/paclitaxel
干预措施: Paclitaxel (Drug)
结局指标
主要结局
MTD of oral continuous dosing of crenolanib (3 different doses) plus ramucirumab/paclitaxel in patients defined as the highest dose level in which <2 of 6 patients develop a DLT. The DLT is based on the 1st cycle adverse events.
时间窗: 5 weeks
The DLT is based on the first cycle (35 days) adverse events. If at least 2 of 3 or 2 of up to 6 patients experience a DLT at the starting dose level, then the study will be paused and the starting dose will be re-assessed. The MTD is defined as the highest dose level in which \<2 of 6 patients develop a DLT. This will constitute the first part of the study which will enroll a maximum of 18 patients.
Response rate (RR) of the combination in patients will be radiographically evaluated until progressive disease (PD), intolerable toxicity, withdrawal of consent, physician's decision, death or the completion of 6 cycles. adenocarcinoma patients
时间窗: Bi-monthly for up to 6 months.
次要结局
未报告次要终点