Chemotherapy for Patients With Gastroesophageal Cancers Who Have Progressed After One Prior Chemo Regimen
A Phase II Study Of Cabazitaxel For Metastatic Gastroesophageal Adenocarcinomas That Have Relapsed After At Least One Line Of Chemotherapy
研究概览
详细说明
Gastric cancer is the second most frequent cancer-related cause of death after lung cancer worldwide with approximately 900,000 cases per year. The incidence of gastric cancer is highest in East Asia, China and Japan. In the last two decades there has been a dramatic increase in North America and Europe of adenocarcinoma of the distal esophagus and GE junction which are indistinguishable from proximal gastric cancer.
Cabazitaxel (XRP6258) is a semi-synthetic novel taxoid. Like traditional taxane drugs, it binds to and stabilizes tubilin structures resulting in inhibition of cold-induced microtubule depolymerization and cell division with subsequent inhibition of tumor cell proliferation. This novel agent, however, has poor affinity for P-glycoprotein--the protein product of multidrug resistance gene ABCB1. P-glycoprotein is a membrane-associated drug efflux pump and is thought to be a potential cause of taxane resistance in tumors. Also unlike traditional taxanes, Cabazitaxel has exhibited penetration through the blood-brain barrier (BBB.) Preclinical studies have demonstrated that Cabazitaxel was cytotoxic for cell lines with acquired resistance to doxorubicin, vincristine, vinblastine, paclitaxel or docetaxel.
Taxanes have demonstrated statistically significant antitumor activity as both monotherapy and as part of combination triplet regimens in gastroesophageal carcinoma.Cabazitaxel has emerged as a novel investigational semi-synthetic taxoid that has established activity in cell lines refractory to traditional taxanes in preclinical studies and now in a phase III study in patients with metastatic prostate cancer. Cabazitaxel, with its low affinity for the P-glycoprotein drug efflux pump, may demonstrate superior response rates to docetaxel. Furthermore, as demonstrated in prostate cancer, cabazitaxel appears to have substantial activity in patients who have previously been treated with docetaxel.
Phase I and II trials have been conducted demonstrating safety and efficacy of Cabazitaxel (XRP6258) in metastatic breast and prostate cancer. Neutropenia was the primary dose-limiting toxicity with the recommended dose established at 20 and 25mg/m2. The latter dose was used in the TROPIC trial, the pivotal phase III trial demonstrating improved overall survival and median progression free survival in patients with hormone resistant prostate cancer refractory to docetaxel who had received Cabazitaxel plus prednisone versus those who received mitaxantrone plus prednisone. Cabazitaxel given at IV doses of 25mg/m2 has demonstrated both safety and anti-tumor efficacy in phase I, II and now phase III trials
The primary goal is to evaluate the activity of Cabazitaxel for the treatment of advanced gastroesophageal cancer that has progressed after at least one line of treatment for metastatic disease. Activity will be defined as a complete or partial response. The investigators will differentiate between a 10% level of activity and a 30% level of activity.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Rhode Island
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Pawtucket、Rhode Island、美国、02860
- Memorial Hospital
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Providence、Rhode Island、美国、02903
- Brown University Oncology Research Group
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Providence、Rhode Island、美国、02906
- Roger Williams
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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
Inclusion Criteria:
- Patients are required to have histologically or pathologically confirmed metastatic gastric or esophageal adenocarcinoma.
- Patients must demonstrate relapse or progression after at least one prior line of chemotherapy for metastatic disease.
- Patients must have measurable disease by CT scan or MRI
- Absolute neutrophil count ≥ 1,500/uL, platelet ≥ 100,000/uL and Hgb > 8.0 g/dl.
- Total bilirubin ≤ upper institutional limit of normal (ULN), and AST or ALT ≤ 3x ULN; if liver metastases then AST or ALT < 5x ULN
- Peripheral neuropathy must be ≤ Grade 1
- Creatinine < 2 x ULN
- ECOG performance status 0 to 2
- Minimum life expectancy of 12 weeks.
- Age older than 18 years.
- Voluntary, signed written informed consent.
- Women of childbearing potential must have a negative pregnancy test Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
Exclusion Criteria:
- History of severe hypersensitivity reaction to Cabazitaxel or other drugs formulated with polysorbate 80.
- Patients with known, untreated brain metastasis
- Any uncontrolled severe, intercurrent illness.
- Women who are breast-feeding.
- Patients who have undergone major surgery, chemotherapy, or radiotherapy within the last 3 weeks.
- Patients on concurrent anticancer therapy
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:real drug
patients will receive Jevtana 25mg/m2, IV every 21 days until disease progression or unacceptable toxicity
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Cabazitaxel 25mg/m2, IV every 21 days until progression
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of Patients Without Progression at 3 Months
大体时间:every three cycles approx every 63 days
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Response will be assessed via RECIST 1.1 criteria
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every three cycles approx every 63 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of Patients Experienced a Toxicity Associated With Cabazitaxel for Patients With Metastatic Gastroesophageal Adenocarcinomas That Have Progressed After at Least One Line of Therapy for Metastatic Disease.
大体时间:During treatment and through 30 days post treatment, approximately 7 months
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CTCAE version 4. It is noted that the time frame was approximately 7 months, taking into account the total amount of treatment patients received on this trial.
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During treatment and through 30 days post treatment, approximately 7 months
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合作者和调查者
出版物和有用的链接
有用的网址
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 (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.
jevtana的临床试验
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M.D. Anderson Cancer Center招聘中
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The Clatterbridge Cancer Centre NHS Foundation...University of Liverpool尚未招聘
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Medical University of South CarolinaPeregrine Pharmaceuticals终止
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Sanofi完全的前列腺癌大韩民国, 西班牙, 美国, 阿根廷, 秘鲁, 罗马尼亚, 台湾, 英国, 比利时, 智利, 荷兰, 澳大利亚, 德国, 突尼斯, 巴西, 加拿大, 法国, 匈牙利, 波兰, 俄罗斯联邦, 南非, 火鸡
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Rahul AggarwalSanofi完全的
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Shanghai Jiao Tong University School of MedicineFudan University; Qilu Hospital of Shandong University招聘中
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Sanofi完全的