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
Overview
- Phase
- Phase 3
- Intervention
- capecitabine
- Conditions
- Breast Cancer
- Sponsor
- Sun Yat-sen University
- Enrollment
- 794
- Locations
- 1
- Primary Endpoint
- Invasive disease-free survival (IDFS)
- Status
- Recruiting
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
wang shusen
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •Stage IV (metastatic) breast cancer
- •History of any prior (ipsi- or contralateral) breast cancer except lobular CIS
- •Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
- •An overall response of PD according to the investigator at the conclusion of preoperative systemic therapy
- •Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
- •History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above
- •Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
- •Current NCI CTCAE (Version 4.0) Grade ≥ 2 peripheral neuropathy
- •History of exposure to the following cumulative doses of anthracyclines:
- •Doxorubicin \>240 mg/m2, Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) \>480 mg/m2 For other anthracyclines, exposure equivalent to doxorubicin \>240 mg/m2
Arms & Interventions
Metronomic Capecitabine Group
Patients in experimental group (also Metronomic Capecitabine Group) will receive additional metronomic chemotherapy of capecitabine (500mg TID po), begin after the completion of standard adjuvant chemotherapy or surgery if neoadjuvant chemotherapy were administrated, until three weeks after the last cycle of trastuzumab (6mg/kg every 3 weeks).
Intervention: capecitabine
Outcomes
Primary Outcomes
Invasive disease-free survival (IDFS)
Time Frame: up to 10 years
Time from randomization to ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death of any cause
Secondary Outcomes
- Invasive disease-free survival including second non-breast cancers(up to 10 years)
- Overall survival(up to 10 years)
- Distant recurrence-free interval(up to 10 years)
- Disease-free survival(up to 10 years)
- Breast cancer specific survival(up to 10 years)