This multi-center, open-label, phase II randomized controlled trial is to evaluate the efficacy of docetaxel(T) combined with metronomic cyclophosphamide/capecitabine (mCX) followed by fluorouracil /epirubicin/cyclophosphamide (FEC) versus T followed by FEC as neoadjuvant chemotherapy in treating women with triple negative breast cancer (TNBC), and to study the anti-tumor immune effect of metronomic neoadjuvant chemotherapy. 186 stage M0 TNBC patients who had a primary tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging are randomly enrolled to receive neoadjuvant T combined with mCX (3 cycles) followed by FEC (3 cycles) or T (3cycles) followed by FEC (3 cycles) before surgery. The primary end point is pathological complete response (pCR) rate, and the secondary end points include: clinical response rate, toxicities, breast-conserving rate, Ki67 and CD31 reduction rate, changes in the percentages of peripheral blood or tumor microenvironmental regulatory T cells (Treg), T helper cells (Th), CD8+ T cell, and tumor-specific CTL, and changes in tumor microenvironmental immune cytokines. Once there is a significant statistical difference in terms of pCR rate between two groups, 3-year disease-free survival (DFS) and 3-year overall survival (OS) will be included in the secondary end points. The aims of this study are to determine whether the neoadjuvant T combined with metronomic CX followed by FEC can significantly increase the pCR rate in TNBC with acceptable toxicity, and to explore the anti-tumor immune effect of metronomic neoadjuvant chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Docetaxel 75mg/m2, iv, d1 or 100mg/m2, iv, d1
Capecitabine 1200mg/m2/d, po, d1-d21
Cyclophosphamide 50 mg/d, po, d1-d21
Fluorouracil 500mg/m2, iv, d1
Epirubicin 100mg/m2, iv, d1
Cyclophosphamide 500mg/m2, iv, d1
Sun Yat-sen Memorial Hospital
Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
Second Xiangya Hospital of Central South University
Changsha, Hunan, China
Xinjiang Medical School Cancer Hospital
Ürümqi, Xinjiang, China
Pathological complete response (pCR) rate
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Ultrasound response rate
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Breast-conserving surgery rate
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)
Tumor Ki67 reduction rate in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Tumor CD31 reduction rate in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Peripheral blood CD8+ T cell percentage change in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Peripheral blood regulatory T cell percentage change in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Peripheral blood tumor specific T cell (CTL) percentage change in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
Peripheral blood T helper cell percentage change in relation to neoadjuvant therapy
Time frame: at definitive surgery (20-24 weeks after the first dose of study medication)
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