Erlotinib in Treating Patients With Breast Cancer That Can Be Removed by Surgery
Phase II Trial of OSI-774 (Tarceva), a Human Epidermal Growth Factor (HER) (erbB, Also Known as Epidermal Growth Factor Receptor, EGFR) Tyrosine Kinase Inhibitor, in Treatment-Naïve Operable Breast Cancer
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with breast cancer that can be removed by surgery.
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
Primary
- To determine the in situ antitumor effect of neoadjuvant erlotinib hydrochloride as measured by a reduction in Ki67 and/or an increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive tumor cells in patients with treatment-naive, operable breast cancer.
Secondary
- To identify a molecular profile, based on measurements of Estrogen Receptor (ER), Epidermal Growth Factor Receptor (EGFR), and a Human Epithelial Growth Factor Receptor-2(HER2), and protein expression profiles in patients with treatment-naïve, operable breast cancer that is responsive to erlotinib hydrochloride.
- To correlate tumor concentrations of erlotinib hydrochloride with serum levels immediately before surgery.
OUTLINE: This is a multi-center study.
Patients receive oral erlotinib hydrochloride once daily for 5-14 days. Patients then undergo surgical resection within 24 hours after the last dose of erlotinib hydrochloride.
Tumor tissue samples are collected at baseline and during surgery for correlative laboratory studies. Tissue samples are stained for ER, HER2, and EGFR levels, proliferation (Ki67), and apoptosis (TUNEL) by immunohistochemistry. Levels of erlotinib hydrochloride in tissue samples are measured by matrix-assisted laser desorption/ionization mass spectrometry. Blood samples are collected on the day of surgery. Levels of erlotinib hydrochloride in blood samples are measured by liquid chromatography/mass spectrometry.
Patients are followed within 6 weeks after surgery.
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
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Alabama
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Birmingham、Alabama、アメリカ、35249
- University of Alabama, Birmingham
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber Cancer Institute
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27514
- Lineberger Comprehensive Cancer Center
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Center
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Nashville、Tennessee、アメリカ、37208
- Meharry Medical College
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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
Inclusion Criteria:
Clinical stage I or II (T1 or T2, N0 or N1) invasive mammary carcinoma
Diagnosis may be made by fine needle aspiration cytology or core biopsy
- A repeat core biopsy is not required for patients who have a paraffin embedded diagnostic core biopsy specimen available for immunohistochemical staining
Exclusion Criteria:
Patients with locally advanced disease who are planning to undergo preoperative neoadjuvant therapy are not eligible*
Locally advanced disease includes any of the following:
- Primary tumor ≥ 5 cm (T3)
- Tumor of any size with direct extension to the chest wall or skin (T4a-c)
- Inflammatory breast cancer (T4d)
- Fixed axillary lymph node metastases (N2)
- Metastasis to ipsilateral internal mammary node (N3) NOTE: *Patients with primary tumors ≥ 5 cm (T3) or tumors involving the chest wall or skin who are not candidates for preoperative chemotherapy or who decline preoperative chemotherapy are eligible
Measurable residual tumor at the primary site
- Measurable disease is defined as any mass that can be reproducibly measured by physical examination
- Planning to undergo surgical treatment with either segmental resection or total mastectomy
- Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer
- No locally recurrent breast cancer
- No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- ANC ≥ 1,000/mm^3
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN
- Serum glutamic oxaloacetic transminase (SGOT) and serum glutamic pyruvic transminase (SGPT) ≤ 1.5 times ULN
- Must be at least 18 years old
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No serious medical illness that, in the judgement of the treating physician, places the patient at high risk of operative mortality
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy for this primary breast cancer
- At least 7 days since prior tamoxifen or raloxifene as a preventive agent
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 |
|---|---|
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実験的：Tarceva
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Tarceva will be given orally at a dose of 150 mg/day for 5-14 days.
Patients are to undergo surgical resection of their tumor within 24 hours of the last dose of Tarceva.
他の名前：
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Used to assess level of expression of genetic markers in pre-therapy and surgical specimens
Used to determine blood plasma levels of Erlotinib on the day of surgery
他の名前：
Used to determine blood plasma levels of Erlotinib on the day of surgery
他の名前：
After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue
他の名前：
Surgical treatment will occur within 24-hours following completion of therapy.
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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 |
|---|---|---|
|
Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva
時間枠：5-14 days
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In situ anti-tumor effect of Tarceva as measured by a minimum 75% reduction in Ki67 compared to pre-treatment tumor cells in patients with operable breast cancer.
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5-14 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Molecular Profile of Participants Who Are Responsive to Tarceva
時間枠：at 5-14 days
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Determined by estrogen receptor status (ER) and human epidermal growth factor receptor 2 (HER2) status, which are measured by staining of 200-500 tumor cells and noting the number stained.
Positive = > 10% of cell show staining, negative = < 10% of cells show staining
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at 5-14 days
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Average Post-treatment Plasma Level of Erlotinib Hydrochloride
時間枠：After last dose of Tarceva, at 5-14 days, and before surgery
|
Post-treatment plasma level in µmol/L of erlotinib hydrochloride
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After last dose of Tarceva, at 5-14 days, and before surgery
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協力者と研究者
捜査官
- スタディチェア：Carlos L. Arteaga, MD、Vanderbilt-Ingram Cancer Center
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
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