A Clinical Trial Evaluating the Effect of ASLAN001 in Patients With Recurrent/Metastatic Gastric Cancer Whose Tumors Are Either HER-2 Amplified or Co-expressing HER-1 and HER-2
Phase II Open Label Study to Evaluate the Biological Activity of ASLAN001 (ARRY 334543) in Patients With Recurrent/Metastatic Gastric, Gastro-oesophageal Junction, and Oesophageal Carcinoma Whose Tumours Are Epidermal Growth Factor Receptor-2 (HER 2) Amplified or Co-expressing Epidermal Growth Factor Receptor-1 (HER-1) and HER-2.
The purpose of this study is to determine whether ASLAN001 has an effect in patients with recurrent or metastatic adenocarcinoma of the stomach, gastrooesophageal junction, or lower third of the oesophagus whose tumours over-express HER-1 and HER-2, or whose tumours are HER-2 gene-amplified.
Maximum of 26 patients will participate in South Korea and the patients will be assigned to either group A or group B according to the results of tests done on tumor tissue obtained by biopsy to determine HER-1 and HER-2 status.
研究概览
详细说明
About 1 million new cases of gastric cancer were estimated to have occurred in 2008 (988,000 cases, 7.8% of the total), making it currently the fourth most common malignancy in the world, behind cancers of the lung, breast, and colo-rectum. Gastric cancer is also the second leading cause of cancer-related death in both sexes worldwide with 700,000 deaths occurring annually. The incidence and mortality rates for gastric cancer vary widely in different regions of the world. The incidence has dramatically declined in the United States where it ranks seventh as a cause of cancer- related deaths. In the Asia-Pacific region, the highest incidences of gastric cancer can be found in China, Japan, and Korea, where the age standardized incidence rate (ASR) is greater than 20 per 100,000 populations. Intermediate risk countries (ASR 11-19/100,000 population) include Malaysia, Singapore, and Taiwan, while low-risk countries (ASR < 10/100,000 population) include Australia, New Zealand, India, and Thailand.
Approximately 95% of all malignant gastric neoplasms are adenocarcinomas. One of the most striking epidemiologic observations has been the increasing incidence of adenocarcinomas involving the proximal stomach and distal oesophagus including the oesophagogastric junction. These tumours are thought to have different etiologic factors; gastric body and antral lesions are associated with low acid production and Helicobacter pylori infection, whereas cardiac lesions are not associated with either.
The treatment for advanced and un-resectable disease has remained essentially unchanged for the past 2 decades, with platinum and fluoro-pyridine-based combination chemotherapy being the mainstay of therapy. The molecular biology responsible for carcinogenesis, tumour biology, and response to therapy in gastric cancer are active areas of investigation. Amplification and/or over-expression of epidermal growth factor receptor-2 (HER 2) have been found to promote tumourigenesis and to be involved in the pathogenesis of gastric cancer. Recently, data from randomised studies of trastuzumab (Herceptin®) in patients with HER 2 amplification demonstrated significant improvement in outcome in comparison to chemotherapy alone. Studies on a number other molecularly targeted agents used alone or in combination with chemotherapy have been undertaken, or are ongoing. Translational research, undertaken as part of these studies, demonstrates the great molecular heterogeneity of the disease, with multiple growth factor and survival pathways being implicated.
In view of this, successful therapeutic intervention is likely to require both the identification of molecularly defined subsets of disease, and the evaluation of rationally-selected combinations of targeted agents.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
-
-
-
Seoul、大韩民国、110-744
- Seoul National University Hospital
-
-
Seoul
-
Bundang、Seoul、大韩民国、463-707
- Seoul National University Hospital
-
-
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
Inclusion Criteria:
- Male or female patients 21 years of age or older at the time written informed consent is obtained.
- Patients with histologically confirmed adenocarcinoma of the stomach, gastro-oesophageal junction or distal oesophagus with inoperable locally-advanced metastatic disease.
- Patients with tumours with immunohistochemical evidence of expression of HER-1 (at level of + or ++ or +++) and HER-2 (at level of + or ++ or +++) using standard criteria OR tumours with gene-amplification of HER-2 by standard FISH.
- Patient has received 1 or more prior chemotherapy for the treatment of adenocarcinoma of the stomach, gastro-oesophageal junction or distal oesophagus with metastatic disease.
- Patients with prior partial gastrectomy if they can take oral medications, and can undergo gastroendoscopic biopsies and meet all other inclusion/exclusion criteria.
- Patients with measurable and non-measurable disease per modified RECIST guidelines. All scans and x-rays used to document measurable or non-measurable disease must be done within a 28-day period prior to enrollment.
- Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 14 days prior to enrolment).
- Patient with adequate organ and haematological function as evidenced by the following laboratory studies within 14 days prior to enrollment:
- Haematological function, as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 75 x 109/L
- Haemoglobin ≥ 9 g/dL
- Coagulation functions, as follows:
- Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limits of normal (ULN) per institutional laboratory normal range
- International normalized ratio (INR) ≤ 1.5
- Renal functions, as follows:
- Serum creatinine ≤ 1.5 x ULN
- Urea ≤ 1.5 x ULN
- Hepatic function, as follows:
- Total bilirubin ≤ 1.5 x ULN
Serum glutamic oxaloacetic transaminase (SGOT)/aspartate transaminase (AST) and serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present)*.
- Except where due to direct disease involvement of the liver at the discretion of the investigator.
Exclusion Criteria:
- Patients unable to swallow oral medications
- Patients with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy.
- Patients who underwent radiotherapy to the gastric remnant ≤ 14 days prior to enrolment. Patients must have recovered from all radiotherapy-related toxicities.
- Patients with total gastrectomy.
- Patients who have uncontrolled, clinically significant symptomatic cardiovascular diseases within 6 months prior to enrolment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure or arrhythmias not controlled by outpatient medication.
- Patients with ongoing or clinically significant active infection as judged by the Investigator.
- Pregnant (i.e., positive beta-human chorionic gonadotropin test) or is breast-feeding women.
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:HER-2 Amplified
|
ASLAN001 500mg BID
|
实验性的:HER-1 & HER-2 Co-expression
|
ASLAN001 500mg BID
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
The percentage of patients demonstrating clear evidence of inhibition of receptor auto-phosphorylation in HER-2 amplified patients on Day 29.
大体时间:Day 29
|
Day 29
|
The percentage of patients demonstrating clear evidence of inhibition of receptor auto-phosphorylation in HER-1 and HER-2 co-expressing patients on Day 29.
大体时间:Day 29
|
Day 29
|
次要结果测量
结果测量 |
大体时间 |
---|---|
The percentage of patients showing inhibition of AKT phosphorylation on Day 29.
大体时间:Day 29
|
Day 29
|
The percentage of patients showing inhibition of MAPK phosphorylation on Day 29.
大体时间:Day 29
|
Day 29
|
The percentage of patients showing inhibition of Ki67 on Day 29.
大体时间:Day 29
|
Day 29
|
The percentage of patients showing induction of apoptosis as measured by TUNEL on Day 29.
大体时间:Day 29
|
Day 29
|
Objective Response Rate
大体时间:Day 57
|
Day 57
|
合作者和调查者
调查人员
- 首席研究员:Seock-Ah Im, Dr.、Seoul National University Hospital
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
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.
ASLAN001的临床试验
-
ASLAN Pharmaceuticals完全的
-
National Cancer Centre, SingaporeNational Medical Research Council (NMRC), Singapore; ASLAN Pharmaceuticals主动,不招人
-
ASLAN PharmaceuticalsSyneos Health; bioRASI, LLC; CMIC Co, Ltd. Japan完全的
-
National University Hospital, Singapore未知