Phase II Study of Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- pathologic complete remission (pCR)
研究概览
简要总结
This is an exploratory interventional study that initiates chemotherapy with letrozole in patients with estrogen receptor positive/HER2-negative breast cancer preoperably.
详细描述
STUDY RATIONALE: Patients with ER+/HER2- operable breast cancers who are candiate of neoadjuant chemotherapy generally receive chemotherapy alone before operation, followed by adjuvant endocrine therapy. Because endocrine therapy is primarily delivered in the postoperative setting, the ability to add the efficacy of aromatase inhibitors combined with chemotherapy is lost. This study offers the unique opportunity to assess the synergistic or additive responsiveness of breast tumors to endocrine therapy plus chemotherapy while the tumors are still in vivo by treating patients with an aromatast inhibitor combined with chemotherapy before surgery and assessing pCR rates.
PRIMARY OBJECTIVE: The primary objective is to determine the frequency of pCR in breast and axilla.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pathologically proven breast cancer patients who are candidate of neoadjuvant chemotherapy with AC followed by Docetaxel
- •Age: 19-70 years
- •ER or PR positive ,cT2-3N0 or cT1-3/N+ M0 (ER-positive ≥1% nuclear staining by immunohistochemistry , Allred score≥3 )
- •Available FFPE tissue for biomarker study
- •HER2-negative by ASCO/CAP guideline
- •Patients who agree to adequate contraception
- •ECOG scores of 0-2
- •Normal or acceptable kidney, liver, cardiovascular, and bone marrow functions
- •Patients who provide consent
排除标准
- •Inflammatory breast cancer
- •Distant metastasis
- •Cerebral vascular accidents including transient ischemic attack
- •Pulmanary thromboembolism or deep vein thrombosis with 6 months; however, patients who received more than 6 weeks of anticoagulation within 6 months and remains asymptomatic are eligible.
- •With a history of malignant tumor or complicated with other malignant tumors in addition to breast cancer, except for non-melanoma skin cancer, curatively resected early gastric cancer, differentiated thyoid cancer < 1 cm, or other cured malignant tumor without recurrence for at least 3 years
- •Ejection Fraction <55% by MUGA scan / Echo CG
- •No available tissue for biomarker study
- •Pregnant or lactating women
- •Patients with other serious diseases or medical conditions: Pituitary adenoma, Malabsorption syndrome, Major resection of gastrointestinal tract, Corrected QT interval > 480 msec, Congestive heart failure or unstable angina pectoris, myocardial infarction, stent insertion, angioplasty, coronary bypass surgery, symptomatic peripheral artery disease within 6 months before the enrollment
- •NYHA class III or IV congestive heart failure
- •Uncontrolled hypertension and uncontrolled high-risk arrhythmia considered by the investigator
- •Major surgery, major trauma, and/or unhealed wound, fracture, or ulcer within 4 weeks
- •Acute hemorrhage or hemorrhagic tendency
- •Obvious neurological or psychiatric disorders, including psychosis, epileptic dementia and other diseases which may affect the understanding and sign of the informed consent
- •Uncontrolled acute infection
- •Patients with allergic constitution and any known or suspected drug allergy
- •Concurrent use of other investigational drugs; or participating in other clinical trials involving investigational drugs within 30 days before this study
- •Patients with mental illness or other conditions affecting the patient compliance
- •Not suitable for the trial considered by the investigator
研究组 & 干预措施
Experimental
Patients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
干预措施: Doxorubicin (Drug)
Experimental
Patients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
干预措施: Cyclophosphamide (Drug)
Experimental
Patients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
干预措施: Docetaxel (Drug)
Experimental
Patients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
干预措施: Letrozole (Drug)
Experimental
Patients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
干预措施: leuprorelin (Drug)
结局指标
主要结局
pathologic complete remission (pCR)
时间窗: within 6 weeks following the last dose of chemotherapy
pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 \[MD Anderson definition\])
次要结局
- Adverse events(during 6 months of neoadjuvant chemotherapy)
- Downstaging to breast conserving surgery (BCS)(within 6 weeks following the last dose of chemotherapy)
- Disease free survival(Patients will be followed up to 6 years)
- Response rate(during 6 months of neoadjuvant chemotherapy)
研究者
Keun Seok Lee
Head, Center for Breast Cancer
National Cancer Center, Korea