Chemotherapy or Letrozole Before Surgery in Treating Postmenopausal Women With Breast Cancer That Can Be Removed By Surgery
A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. It is not yet known whether giving more than one drug (combination chemotherapy) or giving letrozole before surgery is more effective in treating women with breast cancer.
PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before surgery to see how well it works compared with letrozole given before surgery in treating postmenopausal women with breast cancer that can be removed by surgery.
調査の概要
詳細な説明
OBJECTIVES:
- To compare the efficacy and tolerability of cytotoxic chemotherapy versus aromatase inhibition for the down-staging of strongly ER+ primary breast cancer in postmenopausal women.
- To identify biological predictors of response to these two treatment modalities.
OUTLINE: This is a multicenter pilot, feasibility study followed by a randomized study. In the pilot study, a record of all patients screened and invited to participate in the study is compiled. Reasons for failure to recruit will be recorded. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve at least partial response after 3 courses receive docetaxel IV on day 1 of 3-week courses for an additional 3 courses.
- Arm II: Patients receive oral letrozole daily for 18-23 weeks until day of surgery.
Patients in both arms undergo surgery at week 18-23. Most patients then receive adjuvant therapy.
Quality of life is assessed at baseline, periodically during study treatment, and then during follow up.
Blood is collected pre-treatment, at mid-treatment, and before surgery. Blood is then collected every 6 months for 2 years. Blood samples and preserved tumor samples are used for correlative studies.
After completion of surgery, patients are followed up at least annually for 10 years.
PROJECTED ACCRUAL: A total of 40 patients for the pilot study and 716 patients for the phase III study will be accrued.
研究の種類
入学 (予想される)
段階
- フェーズ 3
連絡先と場所
研究場所
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England
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Isleworth、England、イギリス、TW7 6AF
- West Middlesex University Hospital
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London、England、イギリス、W6 8RF
- Charing Cross Hospital
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London、England、イギリス、W2 1NY
- St. Mary's Hospital
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London、England、イギリス、SE1 9RT
- Guy's Hospital
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Seoul、大韓民国、138-736
- Asan Medical Center - University of Ulsan College of Medicine
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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 proven primary invasive breast cancer that is thought to be suitable for neoadjuvant treatment
- No cytological proof of malignancy only
- T2 tumor or greater (≥ 20 mm by ultrasound) or any T stage with nodal disease ≥ 20 mm diameter on ultrasound assessment
- No evidence of distant metastatic disease as disclosed by bone scan, liver, and chest imaging
- Definite indication for neoadjuvant and adjuvant chemotherapy
- Primary tumor amenable to biopsy
- No inoperable disease that is judged very unlikely to be rendered operable by neoadjuvant treatment
- No inflammatory breast cancer
- No bilateral invasive breast cancer
- HER-2 positivity is NOT an exclusion criterion in the feasibility (pilot) study
Estrogen receptor (ER) positive tumor
- No ER-poor disease as defined locally (e.g., H-score < 100, Allred 3/4/5)
- Allred 6/7/8, H-score H ≥100 allowed
PATIENT CHARACTERISTICS:
Postmenopausal, meeting 1 of the following criteria:
- Over 12 months since last menstrual period
- Postmenopausal gonadotrophin levels (luteinizing hormone or follicle-stimulating hormone levels above local criteria)
- Postmenopausal estradiol levels below local criteria
- Prior bilateral oophorectomy
- Menopause induced by gonadotrophin-releasing hormone not allowed
- WHO performance status 0 or 1
- WBC ≥ 3.0 × 10^9/L
- ANC ≥ 1.5 × 10^9/L
- Platelets ≥ 100 × 10^9/L
- Hemoglobin > 9 g/dL
- AST/ALT ≤ 1.5 times upper limit of normal (ULN)
- Serum bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 1.5 times ULN
- Serum creatinine ≤ 1.5 times ULN
- No active, uncontrolled infection
No malignancy within the past 10 years except for basal cell carcinoma or cervical carcinoma in situ
- Treatment for previous malignancy confined to resection alone
- No concomitant medical, psychiatric, or geographic problems that might prevent completion of treatment or follow-up
- No known severe hypersensitivity to aromatase inhibitors
- No contraindication to receiving aromatase inhibitors (clinical evidence or recorded history of osteoporosis)
No other serious illness or medical condition including any of the following:
- Congestive heart failure or unstable angina pectoris
- Myocardial infarction within the past year
- Uncontrolled hypertension or high-risk uncontrolled arrhythmias
- History of significant neurologic or psychiatric disorders, including psychotic disorders, dementia, or seizures, that would prohibit the understanding and giving of informed consent
- Active peptic ulcer
- Unstable diabetes mellitus
- No definite contraindications for the use of corticosteroids
- No contraindication to receiving combination anthracycline/taxane chemotherapy
- Willing to undergo repeat biopsies
PRIOR CONCURRENT THERAPY:
- No hormone replacement therapy within 4 weeks of starting treatment
- No chronic oral treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (≤ 20 mg methylprednisolone or equivalent)
- No concurrent warfarin or heparin therapy
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
- 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:Arm I
Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1.
Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
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与えられた IV
与えられた IV
与えられた IV
与えられた IV
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実験的:Arm II
Patients receive oral letrozole daily for 18-23 weeks until day of surgery.
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経口投与
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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 |
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Feasibility of patient recruitment (pilot)
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Feasibility of tissue collection (pilot)
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Ultrasound (or mammogram) response rate
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二次結果の測定
結果測定 |
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全生存
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生活の質
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無病生存
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臨床反応率
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Radiologic response rate by ultrasound (pilot)
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Pathological complete response rate (pCR) defined as no residual invasive or pre-invasive carcinoma in breast or axilla (pilot)
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Plasma DNA changes in relation to treatment response
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Rate of conservation surgery
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Degree of pathological response
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Ki-67 changes and its relationship to treatment response
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Length of time to maximum response within the treatment period
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Tolerability of the various treatments
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MRI response
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協力者と研究者
スポンサー
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
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
- 代謝拮抗薬、抗腫瘍薬
- 代謝拮抗剤
- 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
- 抗生物質、抗悪性腫瘍薬
- ホルモン拮抗薬
- 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
- ドセタキセル
- シクロホスファミド
- フルオロウラシル
- エピルビシン
- レトロゾール
その他の研究ID番号
- ICCRU-NEOcent-C-21-07
- CDR0000641383 (レジストリ識別子:PDQ (Physician Data Query))
- EU-20936
- EUDRACT-2006-003596-12
- ISRCTN77234840
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。
乳がんの臨床試験
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