卡铂和紫杉醇联合或不联合帕尼单抗治疗浸润性三阴性乳腺癌患者
新辅助卡铂/紫杉醇 (CT) 与帕尼单抗/卡铂/紫杉醇 (PaCT) 联合含蒽环类药物治疗新诊断原发性三阴性炎症性乳腺癌的随机 II 期研究
This randomized phase II trial studies how well carboplatin and paclitaxel with or without panitumumab work in treating patients with invasive triple negative breast cancer. Drugs used in the chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping the them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel with or without panitumumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
研究概览
地位
详细说明
PRIMARY OBJECTIVES:
I. To determine the pathologic complete response (pCR) rate in patients with primary triple-receptor negative (estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2 [HER2]-negative) inflammatory breast cancer (TN-IBC) by using a combination of panitumumab, carboplatin, and paclitaxel (PaCT) in comparison with carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC) in a neoadjuvant setting.
SECONDARY OBJECTIVES:
I. To determine the disease-free survival (DFS) rates produced by either arm of trial combination treatment.
II. To determine the overall survival (OS) rates produced by either arm of trial combination treatment.
III. To determine the safety and tolerability of both arms of trial combination treatment.
EXPLORATORY OBJECTIVES:
I. To determine whether the pCR rate positively correlates with reduced nodal expression status.
II. To determine whether the pCR rate inversely correlates with arginine methylation status of epidermal growth factor receptor (EGFR).
III. To identify molecular biomarkers predictive of the pCR rate by analysis of multiplexed immunohistochemical (IHC) staining.
IV. To identify molecular biomarkers predictive of the pCR rate by genomic and proteomic analysis.
V. To determine whether the inhibition of the EGFR pathway downregulates the COX-2 pathway and mesenchymal marker.
OUTLINE: Patients are randomized into 1 of 2 groups.
GROUP A: Patients receive panitumumab intravenously (IV) over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.
GROUP B: Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up at 1 month and then annually for at least 5 years.
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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Texas
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Houston、Texas、美国、77030
- M D Anderson Cancer Center
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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:
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Patients must have histological confirmation of breast carcinoma
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Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria:
- Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass
- Duration: History of such findings no more than 6 months
- Extent: Erythema occupying at least 1/3 of whole breast
- Pathology: Pathologic confirmation of invasive carcinoma
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Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
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Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%
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Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization
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Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
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Platelet count >= 100 x 10^9/L
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Hemoglobin >= 9.0 g/dL
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Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)
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Alanine aminotransferase (ALT) =< 3.0 x ULN
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Alkaline phosphatase (ALP) =< 2.5 x ULN
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Total bilirubin =< 1.5 x ULN
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Creatinine (Cr) =< 1.5 mg/dL x ULN
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Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault
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Patients have the ability and willingness to sign written informed consent
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Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide
Exclusion Criteria:
- Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible
- History of radiotherapy for current breast cancer diagnosis
- History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ)
- Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
- History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan
- Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with a peripheral neuropathy > grade 1
- Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration
- Patients have a history of prior therapy with carboplatin
- Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
- Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes
- Patients have history of diagnosed interstitial lung disease
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：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：Group A (panitumumab, paclitaxel, carboplatin)
Patients receive panitumumab IV over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. |
Given IV
其他名称：
Given IV
其他名称：
Correlative studies Given IV
其他名称：
|
|
实验性的：Group B (paclitaxel, carboplatin)
Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. |
Given IV
其他名称：
Given IV
其他名称：
Correlative studies |
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 |
|---|---|---|
|
Complete pathologic response
大体时间：At the time of surgery, assessed up to 5 years
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Will be estimated for each treatment arm with exact 95% confidence intervals. A Chi-square test or Fisher's exact test will be used to compare the differences in complete pathologic response rate between the two treatment arms. A logistic regression model will be used to assess the differences in complete pathologic response between the two treatment arms, adjusting for other covariates as appropriate. The analysis will be based on the modified intent-to-treat population. |
At the time of surgery, assessed up to 5 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Disease free survival
大体时间：Up to 5 years
|
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. |
Up to 5 years
|
|
Overall survival
大体时间：Up to 5 years
|
The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. |
Up to 5 years
|
|
Incidence of adverse events
大体时间：Up to 5 years
|
Descriptive statistics will be used. |
Up to 5 years
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Reduced nodal expression status
大体时间：Up to 5 years
|
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used. |
Up to 5 years
|
|
Arginine methylation status of EGFR
大体时间：Up to 5 years
|
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used. |
Up to 5 years
|
|
Molecular biomarkers assessed by genomic and proteomic analysis
大体时间：Up to 5 years
|
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used. |
Up to 5 years
|
|
Downregulation of COX-2 pathway and mesenchymal marker by EGFR pathway
大体时间：Up to 5 years
|
Descriptive statistics will be summarized for all the variables collected in this study. For continuous variables, mean, standard deviation, median, and range will be presented. For categorical variables, frequency tables will be provided. To compare the continuous variables between/among groups, either the parametric method (two-sample t-test or analysis of variance method) or nonparametric method (Wilcoxon or Kruskal-Wallis test) will be used, depending on the distribution of the data. For testing correlation between two categorical variables, either the Chi-square test or Fisher's exact test will be used. |
Up to 5 years
|
合作者和调查者
调查人员
- 首席研究员：Azadeh Nasrazadani、M.D. Anderson Cancer Center
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计的)
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
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 2016-0177
- 2016-0177 (其他标识符：M D Anderson Cancer Center)
- NCI-2017-00619 (注册表标识符：CTRP (Clinical Trial Reporting Program))
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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