A Randomized Phase III Trial Comparing a Neoadjuvant Regimen of FEC-75 Followed by Paclitaxel Plus Trastuzumab With a Neoadjuvant Regimen of Paclitaxel Plus Trastuzumab Followed by FEC-75 Plus Trastuzumab in Patients With HER-2 Positive Operable Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 280
- 试验地点
- 115
- 主要终点
- pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy
研究概览
简要总结
This randomized phase III trial is studying giving fluorouracil together with epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab to see how well it works compared with giving paclitaxel together with trastuzumab followed by fluorouracil, epirubicin, cyclophosphamide, and trastuzumab in treating women with palpable breast cancer that can be removed by surgery. 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. 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. It is not yet known whether it is more effective to give combination chemotherapy before or after treatment with paclitaxel plus trastuzumab.
详细描述
PRIMARY OBJECTIVES:
I. The primary objective of this study is to compare the pathologic complete response rate (pCR) within the breast of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75 (Arm 2), to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab (Arm 1).
SECONDARY OBJECTIVES:
I. To estimate the cardiotoxicity of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75, followed postoperatively by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 2), and compare the cardiotoxicity to that of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab, followed by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 1).
II. To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of invasive adenocarcinoma by core needle biopsy
- •Fine needle aspiration allowed provided primary tumor size < 2 cm and lymph node metastases are present
- •Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph nodes are present
- •Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node
- •HER2-positive disease
- •Confirmation by fluorescent in situ hybridization (FISH) requires gene amplification
- •Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+) staining intensity score
- •Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast regardless of prior therapy allowed
- •Synchronous invasive breast cancer not allowed
- •Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed
- •Those treated with radiation therapy are not allowed
- •No definitive clinical or radiologic evidence of metastatic disease
- •No history of invasive breast cancer
- •Hormone receptor status known
- •Menopausal status not specified
- •ECOG performance status of 0 -1
- •Absolute neutrophil count ≥ 1,200/mm³
- •Platelet count ≥ 100,000/mm³
- •Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal to 1.5 times upper limit of normal [ULN]) resulting from Gilbert disease or similar syndrome due to slow conjugation of bilirubin
- •Alkaline phosphatase ≤ 2.5 times ULN
- •AST ≤ 1.5 times ULN
- •Creatinine normal
- •Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within the past 3 months
- •Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5 times ULN allowed if bone scans fail to demonstrate metastatic disease
- •Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy
- •Prior non-breast malignancies allowed if disease-free for 5 years since completion of initial treatment regimen and deemed by their physician to be at low risk for recurrence
- •Patients who had the following cancers are eligible if diagnosed and treated within the past 5 years:
- •Carcinoma in situ of the cervix
- •Colon carcinoma in situ
- •Melanoma in situ
- •Basal cell and squamous cell carcinoma of the skin
- •No cardiac disease that would preclude the use of epirubicin hydrochloride or trastuzumab (Herceptin®) including any of the following:
- •Active cardiac disease
- •Angina pectoris that requires the use of antianginal medication
- •Cardiac arrhythmia requiring medication
- •Severe conduction abnormality
- •Clinically significant valvular disease
- •Cardiomegaly on chest x-ray
- •Ventricular hypertrophy on EKG
- •Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100 mm/Hg)
- •Patients with hypertension that is well controlled on medication are eligible
- •History of cardiac disease
- •Myocardial infarction documented as a clinical diagnosis or by EKG or any other tests
- •Documented congestive heart failure
- •Documented cardiomyopathy
- •No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0
- •Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy
- •Women of child bearing potential must have a negative urine or serum pregnancy test within 2 weeks of registration
- •Not pregnant or nursing
- •No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
- 另有 10 项未显示
排除标准
- 未提供
研究组 & 干预措施
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Cyclophosphamide (Drug)
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Epirubicin Hydrochloride (Drug)
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Paclitaxel (Drug)
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Therapeutic Conventional Surgery (Procedure)
FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
干预措施: Trastuzumab (Biological)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Cyclophosphamide (Drug)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Epirubicin Hydrochloride (Drug)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Laboratory Biomarker Analysis (Other)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Paclitaxel (Drug)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Therapeutic Conventional Surgery (Procedure)
Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
干预措施: Trastuzumab (Biological)
结局指标
主要结局
pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy
时间窗: Up to 5 years
Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.
次要结局
- LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week(At 12 week)
- Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy(Up to 5 years)
- Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12(Baseline, at 12 week)
- Asymptomatic Decreases From Baseline in LVEF at Week 24(Baseline, at 24 week)
- Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week(Baseline, at 24 week)
- Breast Conservation(From time surgery to up to 5 years)
- Overall Survival (OS)(From time to registration to death, assessed up to 5 years)
- Disease-free Survival (DFS)(From time to registration to time of event, assessed up to 5 years)