Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients
2020年12月16日 更新者：Novartis Pharmaceuticals
A Phase Ib, Open-label, Multicenter, Dose-escalation, Safety and Tolerability Study of LDE225 in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma
This phase Ib study includes two phases: dose escalation phase and safety expansion phase.
During the dose escalation phase, successive cohorts of eligible patients (minimum 3 and maximum 6 evaluable patients per cohort) will receive increasing oral doses of LDE225 administered on a continuous once daily (QD) dose in combination of gemcitabine. This phase of the study will determine the maximum tolerated dose (MTD) and/ or recommended dose for expansion (RDE) of LDE225 administered in combination with gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma patients.
During the safety expansion phase, once the MTD of LDE225 is established, additional patients will be enrolled and treated at the MTD of LDE225 in combination with gemcitabine in order to further evaluate its safety, tolerability and explore the potential efficacy of the combined treatments on the patients in locally advanced or metastatic pancreatic adenocarcinoma.
研究概览
研究类型
介入性
注册 (实际的)
18
阶段
- 阶段1
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
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Massachusetts
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital Dept. of Mass General Hospital
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New York
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New York、New York、美国、10021
- Memorial Sloan Kettering Cancer Center MSKCC - SC
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Utah
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Salt Lake City、Utah、美国、84103
- University of Utah / Huntsman Cancer Institute Huntsman UT
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Liverpool、英国、L7 8XP
- Novartis Investigative Site
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Catalunya
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Barcelona、Catalunya、西班牙、08035
- Novartis Investigative Site
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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
描述
Inclusion Criteria:
- Patients with locally advanced or metastatic pancreatic adenocarcinoma that have not been previously treated or have progressed despite chemotherapy
- Performance status of 0 or 1 per WHO classification
- Adequate hematologic , renal and liver function
- Adequate blood creatine kinase value (CK < 1.5ULN)
Exclusion Criteria:
- Treatment with prior radiotherapy
- Pancreatic cancer that is potentially curable by surgery
- Women of childbearing potential unless they are using highly effective method of contraception Other protocol-defined inclusion/exclusion criteria may apply
Other protocol-defined inclusion/exclusion criteria may apply.
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
- 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：LDE225+gemcitabine
Increasing doses of LDE225 (from 400 mg) once a day + 1000 mg/m2 of gemcitabine on days 1, 8 and 15 of every 28 day cycle.
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Patients will receive increasing doses of LDE225 (from 400 mg), depending on the cohort they are assigned to, orally once daily and standard doses of gemcitabine (1000 mg/m2) on days 1, 8 and 15 of every 28-day cycle.
Patients will receive the study treatment until they progressed, experience unacceptable toxicity, withdraw from the study, or the investigator decides it is in their best interest to discontinue the study treatment.
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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 |
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Incidence rate and category of dose limiting toxicities (DLTs)
大体时间：first 8 weeks of study treatment
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Dose limiting toxicities that occur during the first 8 weeks (56 days) of treatment with LDE225+gemcitabine.
Dose limiting toxicity is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that meets study specific criteria.
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first 8 weeks of study treatment
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Incidence rate of Adverse Events and Serious Adverse Events
大体时间：at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug
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Adverse events and serious adverse events, changes in hematology and chemistry values and assessment of physical and neurological examinations, vital signs and electrocardiograms that occur during the reported period
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at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug
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Plasma pharmacokinetics(PK) parameters of LDE225
大体时间：baseline, week 9 of the study
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Area Under the Curve (AUC), Maximum observed plasma concentration after drug administration (Cmax), Time to reach Cmax (Tmax), etc.
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baseline, week 9 of the study
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Plasma pharmacokinetics (PK) of gemcitabine
大体时间：Baseline, week 9 of the study
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If possible: AUC, Cmax, Tmax, Half life (T1/2), Total body clearance (CL), Apparent volume of distribution at steady state (Vss)
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Baseline, week 9 of the study
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Antitumor efficacy of LDE225+gemcitabine
大体时间：baseline, week 9 of the study
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Efficacy endpoints (Objective response rate and progression free survival) as a function of Hh target gene expression in tumor samples
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baseline, week 9 of the study
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Progression free survival
大体时间：baseline, 8 weeks
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the effect of LDE225+gemcitabine on progression free survival.
Progression Free Survival is defined as the time from date of enrollment to the date of the first documented progression, or death due to any cause, or start of new anti-cancer therapy.
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baseline, 8 weeks
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Objective Response Rate
大体时间：Baseline, 8 weeks
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The effect of LDE225+gemcitabine on objective response rate.
Objective response rate is defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) as their best overall response per RECIST 1.0
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Baseline, 8 weeks
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Duration of Response
大体时间：Baseline, 8 weeks
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The effect of LDE225+gemcitabine on duration of response.
Duration of response is defined as the time from the first occurrence of complete response or partial response until the date of the first documented disease progression or death due to underlying cancer.
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Baseline, 8 weeks
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Serum tumor marker Ca 19-9
大体时间：On Day 1 of every cycle (cycle = 28 days)
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the effect of LDE225+gemcitabine on changes overtime in the serum tumor marker Ca 19-9 levels from baseline as assessed by central lab
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On Day 1 of every cycle (cycle = 28 days)
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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。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
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
2012年3月1日
初级完成 (实际的)
2014年7月1日
研究完成 (实际的)
2014年7月1日
研究注册日期
首次提交
2011年12月5日
首先提交符合 QC 标准的
2011年12月6日
首次发布 (估计)
2011年12月7日
研究记录更新
最后更新发布 (实际的)
2020年12月19日
上次提交的符合 QC 标准的更新
2020年12月16日
最后验证
2016年1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.