Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)
2018年3月7日 更新者：P.O. Witteveen
Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions
The purpose of this study is to determine whether it is possible to predict response to chemotherapy in patients with metastatic cancer who are treated with irinotecan by determining the mutational profile of the tumor.
研究概览
研究类型
观察性的
注册 (实际的)
79
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
-
Utrecht、荷兰、3584 CX
- University Medical Center Utrecht
-
-
North Holland
-
Amsterdam、North Holland、荷兰、1066 CX
- Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
-
-
South Holland
-
Rotterdam、South Holland、荷兰、3075 EA
- Erasmsus Medical Center - Daniël den Hoed clinic
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
概率样本
研究人群
Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.
描述
Inclusion Criteria:
- Patients with a metastatic solid tumor who have failed at least one line of palliative chemotherapy and are irinotecan naïve.
- Patients who are, as per local protocol, eligible for palliative treatment with (standard of care) irinotecan.
- Measurable metastatic lesion(s), according to RECIST 1.1 criteria.
Radiological measurable metastatic lesion(s) of which a histological biopsy can safely be obtained:
- Patients with safely accessible metastases.
- Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
- Patients not using any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID's, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted.
Adequate coagulation status on the day of biopsy as measured by:
- PTT < 1.5 x ULN
- APTT < 1.5 x ULN
- Platelet count 100 x 10*9 / L or higher
- PT-INR < 1.6
- HB > 6
- Biopsies should be performed at least four weeks after last bevacizumab administration.
- Patients age 18 years or up, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.
Exclusion Criteria:
Patients not meeting all of the above inclusion criteria.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
Irinotecan
Patients will be subjected to a their metastatic solid tumor. Radiological response will be evaluated after each 2 cycles: 1. percentage change in radiological volume of the "index lesion" (radiological measurable lesion that underwent biopsy) after the first two cycles of irinotecan; 2. radiological response according to RECIST 1.1 after each 2 cycles. Patients are intended to receive irinotecan until progressive disease or unacceptable toxicity. Patients will be subjected to another biopsy of the index lesion at definitive discontinuation of irinotecan. Patients will also be subjected to blood draws for determining patient's genetic background variation. Side studies include:
|
Histological biopsy of the "index lesion" (a radiological measurable lesion on which biopsy is performed) at baseline, as well as when showing progressive disease.
Histological biopsies will be subjected to DNA sequencing to assess the mutational profile, as well as to analysis of carboxylesterase activity.
其他名称：
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
其他名称：
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
其他名称：
Patients who are being treated in Rotterdam will be subjected to blood draws for validation of the earlier developed midazolam phenotyping test (midazolam clearance test), which may be an indicator for pharmacokinetics of irinotecan.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Exploration of the correlation between the mutational profile and the percentage change in volumetric measurement of the index lesion after the first two cycles of chemotherapy.
大体时间：Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)
|
Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
大体时间：Analysis 6 weeks after initiation of treatment
|
Analysis 6 weeks after initiation of treatment
|
|
Exploration of the correlation between the mutational profile and progression free survival and overall survival.
大体时间：Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
|
Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
|
|
Exploration of the correlation between the mutational profile of the index lesion and patient's germline DNA background variation.
大体时间：Analysis after progressive disease, on average after 3 months.
|
Analysis after progressive disease, on average after 3 months.
|
|
Differences in mutational profile of metastasis prior to and after exposure to treatment.
大体时间：Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
|
Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
|
|
Determine reliable and valid strategies for statistical analysis for biomarker discovery
大体时间：2 years
|
2 years
|
|
Correlate response to pharmacokinetics of SN-38
大体时间：After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
|
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
|
|
Determine carboxylesterase activity in metastatic tumor material (pre- and posttreatment) and correlate intra-tumoral carboxylesterase activity to systemic SN-38 pharmacokinetics and to irinotecan response
大体时间：After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
|
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
|
|
Determine clinical applicability of the midazolam phenotyping probe
大体时间：After first cycle of irinotecan, at three weeks
|
After first cycle of irinotecan, at three weeks
|
|
Number and nature of all (serious) adverse events of study related procedures
大体时间：14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
|
14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Marlies Langenberg, MD/PhD、UMC Utrecht
- 首席研究员：Neeltje Steeghs, MD/PhD、Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
- 首席研究员：Ron Mathijssen, MD/PhD、Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2011年5月1日
初级完成 (实际的)
2015年11月1日
研究完成 (实际的)
2016年8月1日
研究注册日期
首次提交
2011年8月1日
首先提交符合 QC 标准的
2013年5月13日
首次发布 (估计)
2013年5月16日
研究记录更新
最后更新发布 (实际的)
2018年3月9日
上次提交的符合 QC 标准的更新
2018年3月7日
最后验证
2018年3月1日
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.