Randomized Comparison of a Preoperative, Dose-Intensified, Interval-Shortened, Sequential Chemotherapy With Epirubicin, Paclitaxel and CMF ± Darbepoetin Alfa Versus a Preoperative, Sequential Chemotherapy With Epirubicin and Cyclophosphamide Followed by Paclitaxel in Standard Dosage ± Darbepoetin Alfa in Patients With Primary Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 720
- 主要终点
- Relapse-free survival time and overall survival
研究概览
简要总结
The present clinical trial will investigate the efficacy of a sequential interval-shortened and dose-intensified preoperative use of epirubicin, paclitaxel and CMF with preoperative sequential administration of epirubicin and cyclophosphamide followed by paclitaxel in breast cancer. In addition, the influence of darbepoetin alfa on the response rate and quality of life is to be investigated in both treatment arms.
详细描述
Arm A: Sequential treatment in standard doses with Epirubicin (90 mg/m2)/cyclophosphamide (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4×.
Pegfilgratim should be used as secondary preventive after febrile neutropenia in the standard arm of the study, or in exceptional cases also after severe febrile neutropenia necessitating postponement of the treatment by more than one week ± Darbepoetin alfa 1 × 4.5 µg/kg of body weight every two weeks with the start of the first epirubicin dose (day 1) until 14 days after the last dose of paclitaxel Daily oral intake of 200 mg iron unless there complications occur with taking iron
Arm B: sequential dose-intensified, interval-shortened treatment with Epirubicin (150 mg/m2) d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF (600/40/600 mg/m2) d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg after epirubicin and/or paclitaxel: subcutaneous injection on day 2. After CMF pegfilgrastim should be used as a secondary preventive measure
± Darbepoetin alfa 1 × 4.5 µg/kg of body weight every two weeks with the start of the first dose of epirubicin (day 1) until 14 days after the last dose of CMF Daily oral dose of 200 mg iron unless complications occur in taking iron.
Primary goal: Determining the relapse-free survival time and overall survival after dose-intensified sequential preoperative chemotherapy including anthracycline and taxan and/or after preoperative chemotherapy including anthracycline followed by taxan in a standard dose
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
- •Histologically confirmed breast cancer: at least three fast biopsies.
- •Primary tumor ≥2 cm acc. to clinical measurement or manifestation of an inflammatory breast cancer.
- •No systemic metastasis, exclusion by chest x-ray, sonogram of the upper abdomen and skeletal scintiscan.
- •Age ≥18 years and ≤65 years.
- •ECOG < 2/WHO 0-1
- •Adequate organ function defined as SGOT and bilirubin ≤ 1.5× upper limit WBC ≥ 3000 /µL Neutrophils ≥ 1000 /µL Platelets ≥ 100,000 /µL Serum creatinine < 2.0 mg/dL
- •Unremarkable heart echo
- •No florid hepatitis
- •Written consent to participate in the treatment optimization protocol
排除标准
- •Multicentricity in various quadrants (contact the study office)
- •Known allergy to E. coli-produced medication
- •Known allergy to medication containing cremophor (e.g., cyclosporin A)
- •Patients receiving immunosuppressant therapy
- •Lack of consent after informing the patient
- •Lack of willingness to keep and disclose personal medical data as part of the study
- •Pregnancy, nursing
- •Secondary malignancy, excluding basalioma of the skin or carcinoma in situ of the cervix that has received curative therapy
- •Pre-existing treatment-resistant cardiac disease, coronary heart disease, arrhythmias, cardiac insufficiency
- •Patients with uncontrolled hypertension (diastolic >95 mmHg)
- •A history of convulsions
- •Known hypersensitivity to darbepoetin alfa or any of its other ingredients or a known hypersensitivity to r-HuEPO
研究组 & 干预措施
epirubicin, paclitaxel and CMF +/- darbepoetin
Epirubicin (90 mg/m2) d1, q21d - 4× / cyclophosphamide (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4×
+/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first epirubicin dose (day 1) to 14 days after the last dose of paclitaxel
干预措施: Epirubicin, paclitaxel, cyclophosphamide, Methotrexate, 5 FU, darbepoetin alfa (Drug)
EC followed by paclitaxel +/- darbepoetin
Epirubicin (150 mg/m2) d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg, subcutaneous injection on day 2 after epirubicin and/or paclitaxel and secondary prophylactic dose after CMF
+/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first dose of epirubicin (day 1) until 14 days after the last dose of CMF
干预措施: Epirubicin, Cyclophosphamide, Paclitaxel, dabepoetin alfa (Drug)
结局指标
主要结局
Relapse-free survival time and overall survival
时间窗: 2007
次要结局
未报告次要终点