Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca
Phase I/II Study of Abemaciclib + Ramucirumab in Metastatic Esophageal/Gastroesophageal Junction Carcinomas
研究概览
详细说明
This is a multicenter, open label, phase I/II safety study that will enroll 30 subjects with metastatic esophageal and gastroesophageal junction adenocarcinomas post first line systemic chemotherapy. Subjects will be treated with oral Abemaciclib 150 mg PO daily bid given with ramucirumab 8mg/kg every 2 weeks iv until evidence of disease progression or unacceptable toxicities.
A total of 30 subjects will be enrolled. The primary goal is to describe the safety profile of Abemaciclib in combination with Ramucirumab among all enrolled subjects.
If grade 3 or higher treatment-related adverse events occur in 20 subjects, the upper bound of 95% Wilson confidence interval for the adverse event rate would be below 81% (16.7% - 47.9%).
The safety analysis will be performed in all treated subjects. Adverse event data will be listed individually and graded according to the National Cancer Institute Common Terminology Criteria, version 4.03.
Summary statistics will include counts and proportions as well as rates with 95% confidence intervals. Toxicities will be reported as a tabulated table by type and grade.
Objective response rate is defined as the percentage of subjects who achieve an objective response by RECIST1.1 criteria (i.e. Complete response or Partial Response) to Abemaciclib in combination with Ramucirumab. We will estimate the objective response rate, along with the Wilson 95% confidence interval, for the population of subjects.
Overall survival will be defined as the time from study enrollment to death. This will be summarized using a Kaplan-Meier curve.
The proportion of subjects with grade 4 or higher treatment-related adverse events will be monitored continuously throughout the trial using a Bayesian stopping guideline. A Beta (1, 19) prior, representing a toxicity rate of 5%, slightly lower than the expected rate of 6%, was used in the development of our guidelines. The therapy will be re-evaluated if the posterior probability that the toxicity rate exceeds 10% is greater than 75%. Table 3 summarizes the stopping boundaries starting with the initial cohort of 3 subjects through the maximum sample size of 30 subjects.
The probability of triggering the stopping guidelines was assessed for a range of possible toxicity rates using simulations with 5000 replicates. The probability of stopping to re-evaluate was 1% if the true proportion with an unacceptable toxicity was 5%. In comparison, the probability of stopping early was 99.6% if the true proportion with an unacceptable toxicity was 40%
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名:Heather Williams, MS
- 电话号码:(214) 818-7879
- 邮箱:Heather.Williams1@BSWHealth.org
研究联系人备份
- 姓名:Joyce Ghormley
- 电话号码:(214) 818-8961
- 邮箱:Joyce.Ghormley@BSWHealth.org
学习地点
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Texas
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Dallas、Texas、美国、75246
- Baylor University Medical Center, Charles A Sammons Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Subjects must meet all eligibility criteria. The key inclusion and exclusion criteria are as follows:
Key Inclusion Criteria:
- All subjects must have metastatic esophageal or gastroesophageal junction carcinomas (adenocarcinoma only)
- ECOG performance status of 0 or 1
- Tumor tissue must be available for correlative studies - Either a formalin fixed paraffin block or a minimum of ten 5-micron tissue section's (slides) of tumor biopsy sample must be available for biomarker evaluation.
- Patients must have received at least one prior line of standard systemic therapy for recurrent or Stage IV disease, and that patients with HER2 overexpression have received an anti-HER2 drug.
Key Exclusion Criteria:
- Squamous cell carcinomas
- Mixed histology with small cell component
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Abemaciclib plus Ramucirumab
Abemaciclib 150mg dose administered orally twice daily every day plus Ramucirumab dose 8mg/kg iv every 2 weeks until evidence of disease
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150mg dose administered orally twice daily every day
8mg/kg iv every 2 weeks until evidence of disease
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
To describe the safety profile of Abemaciclib + Ramucirumab as assessed according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
大体时间:24 months
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24 months
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次要结果测量
结果测量 |
大体时间 |
---|---|
To assess objective response rate
大体时间:24 months
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24 months
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To assess progression free survival
大体时间:24 months
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24 months
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To assess overall survival
大体时间:24 months
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24 months
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To determine the rate of stable disease at 3 months post targeted therapy
大体时间:24 months
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24 months
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合作者和调查者
调查人员
- 首席研究员:Ronan Kelly, MD、Charles A Sammons Cancer Center/Texas Oncology
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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