Abraxane and Lapatinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
RATIONALE: Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving Abraxane together with lapatinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving Abraxane together with lapatinib works in treating patients with stage I, stage II, or stage III breast cancer.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the clinical response rate, as measured by clinical exam and imaging studies, in patients with stage I-III breast cancer treated with neoadjuvant Abraxane in combination with lapatinib.
Secondary
- Determine the pathologic complete response rate in patients treated with this regimen.
- Correlate proliferation (Ki67), apoptosis (cleaved caspase-3), and angiogenesis (vW, CD34) markers, measured before and after treatment, with tumor response in these patients.
- Conduct other correlative studies, including epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β), before and after treatment with this regimen to assess tumor response in these patients.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a pilot study. Patients are assigned to 1 of 2 treatment groups.
- Group 1: The first 10 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Group 2: The next 20 patients receive Abraxane and lapatinib (at a higher dose) as in group 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection and tumor biopsies periodically for correlative biomarker studies.
PROJECTED ACCRUAL: A total of 30 patients will be accrued to this study.
研究の種類
入学 (実際)
段階
- 初期フェーズ 1
連絡先と場所
研究場所
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Illinois
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Chicago、Illinois、アメリカ、60611-3013
- Northwestern University, Northwestern Medical Faculty Foundation
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Chicago、Illinois、アメリカ、60611
- Hematology-Oncology Associates of Illinois
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Joliet、Illinois、アメリカ、60432
- Midwest Center for Hematology/Oncology
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Olympia Fields、Illinois、アメリカ、60461
- Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
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Texas
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Lubbock、Texas、アメリカ、79410-1894
- Joe Arrington Cancer Research and Treatment Center
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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
DISEASE CHARACTERISTICS:
Histologically confirmed breast cancer
- Clinical stage I-III disease
- Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm with spiral CT scan
- HER2/neu 3+ by immunohistochemistry or positive by fluorescent in situ hybridization
- No known brain metastases
- Hormone receptor status unspecified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Male or female
- Life expectancy > 12 weeks
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500 mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- LVEF ≥ 50% as measured by echocardiogram or MUGA scan
- No other malignancy within the past year
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow and retain oral medication
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
- No ongoing or active infection
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No gastrointestinal (GI) tract disease that would preclude ability to take oral medication
- No malabsorption syndrome
- No requirement for IV alimentation
- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, immunotherapy, radiotherapy, or hormonal therapy for breast cancer
- No prior treatment with epidermal growth factor receptor targeting therapies
- No prior surgical procedures affecting absorption
- No prior surgery for breast cancer
At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
Dexamethasone or dexamethasone equivalent dose ≥ 1.5 mg/day, including any of the following:
- Cortisone (≥ 50 mg/day)
- Hydrocortisone (≥ 40 mg/day)
- Prednisone (≥ 10 mg/day)
- Methylprednisolone (≥ 8 mg/day)
- Phenytoin
- Carbamazepine
- Phenobarbital
- Efavirenz
- Nevirapine
- Rifampin
- Rifabutin
- Rifapentine
- Hypericum perforatum (St. John's wort)
- Modafinil
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
- Clarithromycin
- Erythromycin
- Troleandomycin
- Delavirdine
- Ritonavir
- Indinavir
- Saquinavir
- Nelfinavir
- Amprenavir
- Lopinavir
- Itraconazole
- Ketoconazole
- Voriconazole
- Fluconazole (doses up to 150 mg/day are permitted)
- Nefazodone
- Fluvoxamine
- Verapamil
- Diltiazem
- Cimetidine
- Aprepitant
- Grapefruit or its juice
- At least 6 months since prior and no concurrent amiodarone
At least 2 days since prior and no concurrent gastric pH modifiers*, including any of the following:
- Cimetidine
- Ranitidine
- Nizatidine
- Famotidine
- Omeprazole
- Esomeprazole
- Rabeprazole
- Pantoprazole
- Lansoprazole
- NOTE: *Antacids are allowed within 1 hour before and after administration of study drug
- No other concurrent investigational agents
- No other concurrent anticancer therapy, including chemotherapy, radiotherapy, immunotherapy, or antitumor hormonal therapy
- No concurrent herbal (alternative) medicines
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent bisphosphonates allowed
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:なし
- 介入モデル:単一グループの割り当て
- 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:Treatment arm
30 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
|
Oral lapatinib is taken once daily on days 1-21 of each treatment cycle.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
他の名前:
30 patients receive Abraxane IV over 30 minutes on day 1 each of each treatment cycle.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
他の名前:
|
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 |
---|---|---|
Clinical Response Rate (cRR)
時間枠:At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)
|
cRR measured by RECIST for target lesions assessed by clinical exam+ mammogram+ ultrasound (US). cRR is defined as number of patients who's best response in any of the assessments (clinical exam/mammogram/US) is CR+PR. Response will be defined as one of the following in either clinical exam, mammogram or US: Complete Response (CR)-Disappearance of all target lesions. Partial Response (PR)>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease-neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease <=20% increase in the sum of the 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. |
At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Pathologic Complete Response (pCR)
時間枠:At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery
|
Pathologic Complete Response (pCR) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) and at surgery.
This will be defined as the number of patients that show a pCR after surgery.
pCR is defined as the absence of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.
|
At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery
|
Proliferation (Ki67) Measured at Baseline and After Completion of Study Treatment
時間枠:At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Correlation of proliferation (Ki67) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days).
Ki67 scoring was performed based on degree of staining (0= no staining, 1=weak nuclear staining, 2=moderate nuclear staining, 3=strong nuclear staining).
Ki67 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) Ki67 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
|
At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Apoptosis (Cleaved Caspase-3) Measured at Baseline and After Completion of Study Treatment
時間枠:At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Apoptosis/cleaved caspase-3 (CC3) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days).
Scoring was based on the degree of staining (0=more than 90% of tumor cells with no staining, 1= more than 90% of tumor cells have weak staining, 2= more than 90% of tumor cells have moderate staining, 3= more than 90% of tumor cells have strong staining).
CC3 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) CC3 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
|
At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Angiogenesis (vW, CD34) Markers as Measured at Baseline and After Completion of Study Treatment
時間枠:At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Angiogenesis (vW, CD34) markers will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days). Expressions were analyzed by light microscopy in invasive breast cancer regions. Tumor cells were assigned a score: 0 = no staining
|
At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Epidermal Growth Factor Receptor (EGFR), and Matrix Metalloproteinases (MMPs), Measured at Baseline and After Completion of Study Treatment
時間枠:At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) with expressions analyzed by light microscopy in invasive breast cancer regions. MMP2 cytoplasmic staining intensity was assigned a score: 0=no reactivity,
Greater than or equal to 2+ score was considered positive for expression. EGFR membrane staining was assigned a score: 0 = no staining or faint staining in less than 10% of cells
|
At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
|
Side Effects From the Combination of Abraxane and Lapatinib
時間枠:At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
|
Side effects from the combination of Abraxane and Lapatinib will be assessed using CTCAE 3.0. Side effects that were related to study treatment and grade 3 or higher were collected where: Grade 1= Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life-threatening Grade 5 = Death |
At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Circulating Tumor Cell Measurement
時間枠:At baseline, then before each study treatment cycle begins (1 cycle = 21 days)
|
Circulating tumor cell measurement will be assessed by lab tests done at baseline, then before each study treatment cycle begins (1 cycle = 21 days)
|
At baseline, then before each study treatment cycle begins (1 cycle = 21 days)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Virginia G. Kaklamani, MD、Northwestern University
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 (実際)
研究の完了 (実際)
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 (見積もり)
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
- NU 05B2 (その他の識別子:Northwestern University)
- STU00007257 (その他の識別子:Northwestern University IRB)
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。
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