浸潤性トリプルネガティブ乳がん患者の治療におけるパニツムマブ併用または非併用のカルボプラチンおよびパクリタキセル
新たに診断された原発性トリプルネガティブ炎症性乳癌に対するネオアジュバント カルボプラチン/パクリタキセル (CT) 対パニツムマブ/カルボプラチン/パクリタキセル (PaCT) とその後のアントラサイクリン含有レジメンの無作為化第 II 相試験
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Texas
-
Houston、Texas、アメリカ、77030
- M D Anderson Cancer Center
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
-
Patients must have histological confirmation of breast carcinoma
-
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
-
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
-
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%
-
Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization
-
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
-
Platelet count >= 100 x 10^9/L
-
Hemoglobin >= 9.0 g/dL
-
Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)
-
Alanine aminotransferase (ALT) =< 3.0 x ULN
-
Alkaline phosphatase (ALP) =< 2.5 x ULN
-
Total bilirubin =< 1.5 x ULN
-
Creatinine (Cr) =< 1.5 mg/dL x ULN
-
Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault
-
Patients have the ability and willingness to sign written informed consent
-
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
他の名前：
Given IV
他の名前：
Correlative studies Given IV
他の名前：
|
|
実験的：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
他の名前：
Given IV
他の名前：
Correlative studies |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Complete pathologic response
時間枠：At the time of surgery, assessed up to 5 years
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Disease free survival
時間枠：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
時間枠：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
時間枠：Up to 5 years
|
Descriptive statistics will be used. |
Up to 5 years
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Reduced nodal expression status
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Azadeh Nasrazadani、M.D. Anderson Cancer Center
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (推定)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2016-0177
- 2016-0177 (その他の識別子：M D Anderson Cancer Center)
- NCI-2017-00619 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。