A Randomized Phase III Study Comparing Docetaxel Followed by Cyclophosphamide, Epirubicin and 5-FU to Docetaxel With Capecitabine Followed by Cyclophosphamide, Epirubicin and Capecitabine as Adjuvant Treatment for Early Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,500
- 试验地点
- 2
- 主要终点
- Recurrence-free survival
研究概览
简要总结
This study compares two chemotherapy regimens as adjuvant treatment for breast cancer. The study participants are randomly allocated to receive either 3 cycles of docetaxel followed by 3 cycles of CEF (cyclophosphamide, epirubicin and 5-fluorouracil) or to receive 3 cycles of docetaxel plus capecitabine followed by 3 cycles of CEX (cyclophosphamide, epirubicin and capecitabine). The study participants are required to to have a medium to high risk for breast cancer recurrence. The primary aim of the study is to investigate whether addition of capecitabine to a standard taxane/anthracycline regimen will influence recurrence-free survival.
详细描述
This is an open-label, two-arm, randomized multi-center phase III trial to compare efficacy and safety of a taxane-anthracycline regimen to a taxane-anthracycline-capecitabine regimen as adjuvant treatment of early breast cancer with an intermediate-to-high risk of cancer recurrence.
Patients diagnosed with early breast cancer with an estimated risk of 25% or greater for distant recurrence within 5 years from the diagnosis will be randomly allocated to one of the following 2 arms (1:1):
- Arm A -- 3 cycles of docetaxel 80 mg/m² intravenous (i.v.) (repeated on day [d.] 22); followed by 3 cycles of CEF (cyclophosphamide 600 mg/m2 i.v., epirubicin 75mg/m² i.v., 5-fluorouracil 600 mg/m2 i.v., repeated on d. 22)
- Arm B -- 3 cycles of TX (docetaxel 60 mg/m² i.v., capecitabine twice daily 900 mg/m² given orally on days 1-15 of the cycle; cycle repeated on d. 22); followed by 3 cycles of CEX (cyclophosphamide 600 mg/m2 i.v., epirubicin 75mg/m² i.v, capecitabine twice daily 900 mg/m² on days 1-15 of the cycle; cycle repeated on d. 22)
Locoregional radiotherapy is given according to the institutional practice after completing adjuvant chemotherapy (Tx3/CEFx3 or TXx3/CEXx3).
All patients with ER and/or PgR positive disease will receive adjuvant endocrine therapy. This will consist of 1 mg p.o. anastrozole (ArimidexR) given for 60 months in women who were post-menopausal prior to chemotherapy (no menstrual periods for > 6 months) or of tamoxifen 20 mg p.o. for 60 months in women who were pre-menopausal prior to chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •To be eligible for inclusion in the study, each patient must fulfill each of the criteria below.
- •Have provided written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
- •Be female and 18 years of age or older.
- •Have histologically confirmed invasive breast cancer.
- •High risk of breast cancer recurrence (> 25% within the first 5 years without adjuvant therapy, > 35% within the first 10 years) with one of the following:
- •Regional node positive disease (pN+; tumor cells or tumor cell clusters < 0.2 mm in diameter are not counted as metastases);
- •Pathological N0 and PgR- and tumor size > 20 mm.
排除标准
- •Patients who fulfill any of the following criteria will be excluded:
- •> 65 years of age.
- •"Special type" histology (mucinous, papillary, medullary, or tubular breast cancer), when pN
- •ER, PgR and HER-2 status (via in situ hybridization or immunohistochemistry) not determined.
- •Presence of distant metastases.
- •Previous chemotherapy in the neoadjuvant setting.
- •Non-ambulatory or WHO performance status >
- •Pregnant or lactating women. Women of childbearing potential (menstruating within 6 months of study entry or with no hysterectomy and age < 55) with either a positive or no pregnancy test at baseline.
- •Women of childbearing potential unless using a reliable and appropriate contraceptive method. (Post-menopausal women must have been amenorrheic for at least 6 months to be considered of non-childbearing potential).
- •More than 12 weeks between breast surgery and date of randomization.
- •Organ allografts with immunosuppressive therapy required.
- •Major surgery (except breast surgery) within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.
- •Participation in any investigational drug study within 4 weeks preceding treatment start.
- •Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.
- •History of another malignancy within the last five years except cured basal cell carcinoma of skin or carcinoma in situ of the uterine cervix.
- •Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.
- •Abnormal laboratory values:
- •Hemoglobin < 10.0 g/dL, neutrophils < 1.5 x 10^9/L, platelet count < 120 x 10^9/L;
- •Serum creatinine > 1.5 x Upper Limit of Normal (ULN);
- •Creatinine clearance (calculated per Cockroft and Gault) < 50 mL/min;
- •Serum bilirubin > ULN;
- •ALAT > 1.5 x ULN;
- •Alkaline phosphatase > 2.5 x ULN.
- •Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease.
- •Lack of physical integrity of the upper gastrointestinal tract or those who have clinically significant malabsorption syndrome.
- •Inability to swallow tablets.
- •Life expectancy of less than 3 months.
- •Unwilling or unable to comply with the protocol for the duration of the study.
- •Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
结局指标
主要结局
Recurrence-free survival
次要结局
- Adverse event rate (CTCAE v. 3.0)
- Overall survival