Ruxolitinib in Patients With Breast Cancer
2017年1月3日 更新者：Nancy Lin, MD、Dana-Farber Cancer Institute
Phase II Study of Ruxolitinib (INCB018424) in Patients With PSTAT3+ Breast Cancer
Ruxolitinib is a drug which blocks the Janus tyrosine Kinase (JAK) signaling pathway.
It is thought that this pathway might be important in certain types of breast cancer, and that blocking this pathway might lead to anti-cancer effects.
This study is testing the effects of ruxolitinib in patients with breast cancer.
研究概览
详细说明
Objectives:
Primary
- The primary objective of this two-stage, phase II study is to estimate the objective response rate to ruxolitinib in patients with metastatic or unresectable locally advanced breast cancer which is pStat3+ and which has progressed on at least one line of chemotherapy for advanced disease, and/or has recurred within 12 months of completion of neoadjuvant/adjuvant chemotherapy.
Secondary
- To describe the toxicity profile
- To evaluate clinical benefit rate (CR + PR + SD >/= 24 weeks)
- To estimate progression-free and overall survival
Exploratory
- To explore whether baseline hs-CRP level higher than the group median is associated with objective response
- To explore whether baseline IL-6 level higher than the group median is associated with objective response
- To describe hs-CRP level over time, and to describe the proportion of patients with a) hs-CRP > 3mg/L at baseline, on treatment, and at time of progression, and b) hs-CRP > 1mg/L at baseline, on treatment, and at time of progression
- To describe IL-6 level over time, and to describe the proportion of patients with IL-6 level above the upper limit of normal at baseline, on treatment, and at time of progression
- To describe pStat3 status by IHC in baseline metastatic biopsies
- To describe pStat3 status by IHC in on-study biopsies
- To describe pStat3 status by IHC in the time of progression biopsy samples
- To characterize archival and metastatic biopsy samples using triple immunofluorescence for CD44, CD24, and pStat3
- To characterize archival and metastatic biopsy samples using a previously characterized pStat3 gene signature
- To characterize circulating tumor cells (CTCs) for CD44, CD24, and pStat3 at baseline and time of progression
研究类型
介入性
注册 (实际的)
21
阶段
- 阶段2
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、02215
- Dana-Farber Cancer Institute
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital
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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:
- Histologically or cytologically confirmed invasive breast cancer
- Must have known ER, PR and HER2 status
- Either, Triple Negative Metastatic Breast Cancer or
- Inflammatory Breast Cancer with any ER, PR HER2 status
- Availability of archival tissue specimen suitable for pStat3 testing
- Life expectancy of greater than 3 months
- Measurable disease by RECIST
- At least one prior chemotherapy regimen for treatment of metastatic breast cancer and/or recurrence within 12 months of completion of neoadjuvant/adjuvant chemotherapy or
- For patients with inflammatory breast cancer but no distant metastases, progression through standard neoadjuvant chemotherapy is required
Exclusion Criteria:
- Pregnant or breastfeeding
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
- Clinically significant malabsorption syndrome
- Concurrent use of medications/substances that are strong inhibitors of CY3A4
- No uncontrolled intercurrent illness
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：非随机化
- 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：Ruxolitinib-Cohort A
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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其他名称：
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实验性的：Ruxolitinib-Cohort B
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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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 |
|---|---|---|
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Objective Response Rate
大体时间：Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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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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Clinical Benefit Rate
大体时间：Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions.
Stable disease (SD) is defined as any condition not meeting the above criteria.
SD needed to be a minimum 24 weeks in duration.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Overall Survival
大体时间：In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-Free Survival
大体时间：Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death.
Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.
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Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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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。
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6月1日
初级完成 (实际的)
2015年6月1日
研究完成 (实际的)
2016年6月1日
研究注册日期
首次提交
2012年3月20日
首先提交符合 QC 标准的
2012年3月22日
首次发布 (估计)
2012年3月26日
研究记录更新
最后更新发布 (实际的)
2017年2月23日
上次提交的符合 QC 标准的更新
2017年1月3日
最后验证
2017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.