A Randomized, Multicenter, Open-label Phase III Study to Evaluate the Efficacy and Safety of Adding Metronomic Chemotherapy of Capecitabine to Standard Adjuvant Therapy for Patients With High Risk HER2-positive Primary Breast Cancer
Breast cancer is the most common malignant tumor in women. Recurrent or metastatic breast cancer is incurable. High risk patients usually have the following characteristics, such as, non-pCR after neoadjuvant therapy, lymph nodes positive, \>2cm tumor size, HER2 overexpression, etc. Intensive targeted or chemo therapy could improve prognosis. Previous studies have shown the efficacy and feasibility of intensive treatment of capecitabine in non-pCR breast cancer patients. Given the metronomic capecitabine therapy is well tolerated, we designed this study to compare the efficacy and safety of adding metronomic capecitabine to standard adjuvant therapy for high risk HER2+ breast cancer patients.
• Early stage operable HER2-positive primary breast cancer
• Histologically confirmed invasive breast carcinoma
• High risk patients: residual invasive lesions in surgical specimens after neoadjuvant treatment (non-pCR ), Lymph node positive, tumor maximal diameter \>2cm. If patient get neoadjuvant treatment, Systemic therapy must consist of at least 6 cycles of chemotherapy, with a total duration at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based chemotherapy. Patients may have received an anthracycline as part of preoperative therapy in addition to taxane chemotherapy. Patients receiving dose-dense chemotherapy regimens are eligible, provided at least 8 weeks of taxane-based therapy and at least 8 weeks of trastuzumab have been given.
• Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes
• Known hormone receptor status
• Signed written informed consent approved by the study site's Institutional Review Board (IRB)/Ethical Committee (EC)
• Age ≥ 18 years, Age ≤ 70 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate organ function during screening, defined as:
‣ Absolute neutrophil count ≥ 1200 cells/mm3
⁃ Platelet count ≥ 100000 cells/mm3
⁃ Hemoglobin ≥ 9.0 g/dL; patients may receive red blood cell transfusions to obtain this level
⁃ Serum creatinine 1.5 upper limit of normal (ULN)
⁃ International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN
⁃ Serum AST and ALT ≤ 1.5 ULN
⁃ Serum total bilirubin (TBILI) ≤ 1.0 ULN (within normal limits), except for patients with Gilbert's syndrome, for whom direct bilirubin should be within the normal range
⁃ Serum alkaline phosphatase (ALK) ≤ 1.5 ULN
⁃ Screening LVEF ≥ 50% on ECHO or MUGA after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be ≥ 55% after completion of neoadjuvant chemotherapy.
• i. LVEF assessment may be repeated once up to 3 weeks following the initial screening assessment to assess eligibility.
• For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 7 months after the last dose of study drug.
• Negative serum pregnancy test for premenopausal women including women who have had a tubal ligation and for women less than 12 months after the onset of menopause
• Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes HB surface antigen (HBsAg) and/or total HB core antibody (anti-HBc) in addition to HCV antibody testing. The most recent serologic testing must have occurred within 3 months prior to initiation of neoadjuvant therapy. If such testing has not been done, it must be performed during screening.