Docetaxel, Epirubicin, and Cyclophosphamide With or Without Trastuzumab in Treating Women With Locally Advanced Breast Cancer That Can Be Removed By Surgery
Evaluation of Response Rate to Pre-Operative Docetaxel + Herceptin Study Part A and Docetaxel Study Part B in Locally Advanced Breast Cancer Patients, Stratified by HER2-Status Trial - PHASE II [(Herceptin Docetaxel Neoadjuvant) HEDON]
RATIONALE: Drugs used in chemotherapy, such as docetaxel, epirubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy with or without monoclonal antibody therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving docetaxel, epirubicin, and cyclophosphamide with or without trastuzumab works in treating women with locally advanced breast cancer that can be removed by surgery.
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
- Determine the efficacy of neoadjuvant therapy comprising docetaxel and trastuzumab (Herceptin®) and adjuvant therapy comprising epirubicin hydrochloride, cyclophosphamide, and trastuzumab (Herceptin®) followed by radiotherapy in women with locally advanced, HER2-positive, operable breast cancer.
- Determine the efficacy of neoadjuvant therapy with docetaxel and adjuvant therapy comprising epirubicin hydrochloride and cyclophosphamide followed by radiotherapy in women with locally advanced, HER2-negative, operable breast cancer.
OUTLINE: This is an open-label, prospective, multicenter study. Patients are stratified according to HER2 status (positive vs negative).
Neoadjuvant therapy:
- Stratum 1 (HER2-positive disease): Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, and 15 and docetaxel IV over 60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity
- Stratum 2 (HER2-negative disease): Patients receive docetaxel IV alone as in stratum 1.
- Surgery: All patients undergo surgery in week 19.
Adjuvant therapy: Beginning within 2 weeks after surgery, patients receive adjuvant therapy.
- Stratum 1 (HER2-positive disease): Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, and 15, epirubicin hydrochloride IV over 30 minutes on day 2, and cyclophosphamide IV over 30 minutes on day 2. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV alone every 3 weeks until week 52.
- Stratum 2 (HER2-negative disease): Patients receive epirubicin hydrochloride and cyclophosphamide as in stratum 1.
- Radiotherapy: Patients who undergo breast conserving surgery or patients who undergo mastectomy with ypN positive lymph nodes (i.e., > 4 positive lymph nodes) or ypT3 tumor (i.e., tumor size > 4 cm) undergo radiotherapy, beginning in approximately week 31 and continuing until up to week 38.
- Adjuvant endocrine therapy: Patients with estrogen receptor- or progesterone receptor-positive disease receive adjuvant endocrine therapy beginning in approximately week 31. Premenopausal patients ≤ 40 years of age receive goserelin for 2-3 years and tamoxifen citrate for 5 years.Premenopausal patients > 40 years of age receive tamoxifen citrate for 5 years. Postmenopausal patients receive anastrozole for 5 years years.
After completion of study treatment, patients are followed periodically for up to 5 years.
PROJECTED ACCRUAL: A total of 94 patients will be accrued for this study.
研究の種類
入学 (予想される)
段階
- フェーズ2
連絡先と場所
研究場所
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Bayreuth、ドイツ、D 95448
- Klinikum Bayreuth
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Cologne、ドイツ、D-50391
- Universitaetsfrauenklinik - Koeln
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Deggendorf、ドイツ、94469
- Klinikum Deggendorf
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Jena、ドイツ、D-07743
- Klinikum der Friedrich-Schiller Universitaet Jena
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Munich、ドイツ、D-81675
- Klinikum Rechts der Isar - Technische Universitaet Muenchen
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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 or cytologically confirmed primary carcinoma of the breast by core biopsy
Solitaire or multifocal disease, defined as tumor manifestations within a quadrant or distance between tumor manifestations measured bilaterally < 4 cm, respectively
- No multifocal primary tumor, defined as tumor manifestations in different quadrants or distance between tumor manifestations ≥ 4 cm
Locally advanced, operable disease
Primary tumor ≥ 2 cm by clinical examination or imaging (i.e., mammogram, MRI, or ultrasound)
- Inflammatory breast cancer with bidimensionally measurable lesion, independent of nodal status, allowed
HER2 status meeting 1 of the following criteria:
HER2-positive disease
- 3+ by immunohistochemistry (IHC) and/or positive by fluorescence in situ hybridization (FISH)
HER-2 negative disease
- 0 or 1+ by IHC OR 2+ by IHC and negative by FISH
- No distant metastases by clinical or imaging diagnosis
- No prior breast cancer
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Female
- Pre- or post-menopausal
- ECOG performance status 0-2
- Platelet count ≥ 100,000/mm^3
- Neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 10 g/dL
- ALT and AST ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN
- Bilirubin normal (unless due to clearly documented Gilbert's syndrome)
- Not pregnant or nursing
- Negative pregnancy test (for premenopausal women or women with a postmenopausal status for < 1 year)
- Fertile patients must use effective contraception
- Adequate organ function for cytotoxic chemotherapy
- No known hypersensitivity reaction to the study agents or incorporated substances
- No known allergy or severe reactions to trastuzumab or its constituents (for patients with HER2-positive disease)
- No preexisting motor or sensory neuropathy ≥ grade 2
- No other invasive malignancy within the past 5 years that would preclude study compliance or affect the interpretation of study results
- LVEF ≥ 55% by MUGA or echocardiography
No other serious illness or medical condition, including any of the following:
- New York Heart Association class II-IV congestive heart failure
- History of documented congestive heart failure
- Unstable angina pectoris
- Myocardial infarction within the past 12 months
- Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
- Clinically significant valvular heart disease
- High-risk, uncontrolled arrhythmias
- Dyspnea at rest due to malignant or other disease
- Condition that requires supportive oxygen therapy
- Active serious uncontrolled infections
- Uncontrolled diabetes
PRIOR CONCURRENT THERAPY:
- No prior systemic therapy for cancer
- No prior trastuzumab (Herceptin^®) (for HER2-positive patients)
- No other concurrent anticancer therapy
- No other concurrent investigational drugs
- No concurrent immunosuppressive therapy
- No concurrent sex hormones
- No concurrent corticosteroids unless for premedication
- No concurrent bisphosphonates during active treatment with chemotherapy
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
- マスキング:なし(オープンラベル)
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 |
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予測マーカーの同定
|
|
Rate of pathologic complete remission (pCR) after neoadjuvant therapy comprising docetaxel and trastuzumab (Herceptin®) in women with locally advanced, HER2-positive, operable breast cancer
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Rate of pCR after neoadjuvant docetaxel in women with locally advanced, HER2-negative, operable breast cancer
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Tolerability of treatment as measured by the nature and frequency of adverse events in women with HER2-positive or HER2-negative disease
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二次結果の測定
結果測定 |
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Rate of breast conserving therapy versus mastectomy in comparison to preoperative evaluation
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Correlation of clinical/sonographical response with pathological response, including lymph node status
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Rate of clinical complete remission (cCR) after neoadjuvant therapy comprising docetaxel and trastuzumab in women with locally advanced, HER2-positive, operable breast cancer
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Rate of cCR after neoadjuvant docetaxel in women with locally advanced, HER2-negative, operable breast cancer
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Disease-free survival after 2.5 and 5 years
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Overall-survival after 2.5 and 5 years
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協力者と研究者
捜査官
- スタディチェア:Stefan Paepke, MD、Technical University of Munich
研究記録日
主要日程の研究
研究開始
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
本研究に関する用語
追加の関連 MeSH 用語
- 皮膚疾患
- 新生物
- 部位別新生物
- 乳房の病気
- 乳房腫瘍
- 薬の生理作用
- 薬理作用の分子機構
- 酵素阻害剤
- 抗リウマチ剤
- 抗悪性腫瘍薬
- 免疫抑制剤
- 免疫学的要因
- チューブリンモジュレーター
- 抗有糸分裂剤
- 有糸分裂モジュレーター
- ホルモン、ホルモン代替物、およびホルモン拮抗薬
- 抗腫瘍剤、ホルモン剤
- 抗悪性腫瘍薬、アルキル化
- アルキル化剤
- 骨髄破壊的アゴニスト
- トポイソメラーゼ II 阻害剤
- トポイソメラーゼ阻害剤
- 抗悪性腫瘍剤、免疫
- 抗生物質、抗悪性腫瘍薬
- ホルモン拮抗薬
- 骨密度維持剤
- アロマターゼ阻害剤
- ステロイド合成阻害剤
- エストロゲン拮抗薬
- 選択的エストロゲン受容体モジュレーター
- エストロゲン受容体モジュレーター
- ドセタキセル
- シクロホスファミド
- トラスツズマブ
- エピルビシン
- ゴセレリン
- タモキシフェン
- アナストロゾール
その他の研究ID番号
- CDR0000516034
- KRDI-TUM-HED-324-PAE-0090-I
- EU-20634
- EUDRACT-2005-000967-24
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。