A Prospective， Randomized， Open-label， Multicentric，phaseIII Clinical Trial Compared With PC and CEF100 Followed by Docetaxel as Adjuvant Chemotherapy Regimen for Chinese Primary Triple Negative Breast Cancer Patients
Overview
- Phase
- Phase 3
- Intervention
- Paclitaxel Cisplatin
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- Fudan University
- Enrollment
- 647
- Primary Endpoint
- disease-free survival
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Previous studies in Western country show that triple-negative breast cancer has aggressive clinical and pathological features compared with non-triple negative breast cancer, including onset at a young age, advanced clinical stage, high histologic and nuclear grade and more distant recurrence.
According to the characteristics of triple negative breast tumor, the TNBC patients can benefit neither from hormonal therapies nor from target therapies against Her2 receptors. The only systemic therapy currently available is chemotherapy, and prognosis remains poor. It becomes more and more important to investigate the sensitive chemotherapy regimen for triple negative patients.
Cisplatin-based regimen was active for the patients of lung cancer, colorectal cancer and ect. Triple negative breast cancer patients were more sensitive to platinum-based chemotherapy regimens according to the results of some retrospective studies.
The investigators hypothesized that paclitaxel combined with cisplatin is more sensitive to triple negative breast cancer compared with CEF followed by docetaxel.
Detailed Description
Eligibility Female adults(18-70 years old) are eligible if they had histologically confirmed primary breast cancer. Patients also had Eastern Cooperative Oncology Group(ECOG) Performance status of 0 or 1, absolute neutrophil count (ANC)\>1500/mm3,hemoglobin \>90g/dL, and platelet count \>100,000/mm3,creatinine\<2.5 times the upper limit of normal(ULN)）, transaminases\<3 times ULN or alkaline phosphatase\<4 times ULN if transaminases was normal, and total bilirubin \<1.5 times ULN. Exclusion criteria were active infection, pregnancy, other primary malignancy (except in situ carcinoma of cervix or adequately treated nonmelanomatous carcinoma of the skin), any documented distant metastasis and uncontrolled systemic diseases. This study protocol was approved by institutional ethic review boards and conducted according to guidelines for good clinical practice and the Helsinki Declaration.All patients provided written informed consent. Outcome Measures Primary Endpoint：5 year Disease Free Survival（DFS） Second Endpoints：5 year distant disease free survival （DDFS） 5 year event free survival （EFS） 5 year overall survival （OS） 5 year DFS in gBRCA1 mutation carriers and homologous recombination repair (HRR)-related gene mutation carriers
Investigators
Zhimin Shao
professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Women aged from 18 to 70 years;
- •Histologically proven invasive unilateral breast cancer (regardless of the type);
- •Initial clinical condition compatible with complete initial resection;
- •No residual macro or microscopic tumor after surgical excision;
- •Beginning of chemotherapeutic treatment no later than day 42 after the initial surgery;
- •positive lymph node or negative lymph node with tumor size \> 1.0cm
- •Patient presenting one of the following criteria (reviewed before randomization by referent pathologist):
- •Triple negative （ER-PR-Her-2-） Hormone receptor negativity is defined as ER\<1%, PR\<1% (IHC), HER2 negativity is defined as IHC 0-1+, or \[IHC 2+ and FISH or CISH negative\].
- •No clinically or radiologically detectable metastases (M0);
- •No peripheral neuropathy \> 1;
Exclusion Criteria
- •Bilateral breast cancer or patient with controlateral DCIS;
- •Any metastatic impairment, including homolateral sub-clavicular node involvement,regardless of its type;
- •Any T4 lesion (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer);
- •ER+ or PR+ or Her-2 overexpression
- •Any clinically or radiologically suspect and non-explored damage to the controlateral breast;
- •Any chemotherapy, hormonal therapy or radiotherapy before surgery;
- •Previous cancer (excepted cutaneous baso-cellular epithelioma or uterin peripheral ephitelioma) in the preceding 5 years, including invasive controlateral breast cancer;
- •Patients already included in another therapeutic trial involving an experimental drug;
- •Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study;
- •LEVF \< 50% (MUGA scan or echocardiography);
Arms & Interventions
6 cycles of PC adjuvant chemotherapy
paclitaxel 80 mg/m2 and carboplatin (area under the curve \[AUC\]= 2) on day 1, 8, 15 every 28 days for six cycles
Intervention: Paclitaxel Cisplatin
3 cycles of FEC followed by 3 cycles of Docetaxel
fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 intravenously on day 1 every 21 days for three cycles followed by docetaxel 100 mg/m2 intravenously
Intervention: fluorouracil epirubicin cyclophosphamide and docetaxel (FEC-T)
Outcomes
Primary Outcomes
disease-free survival
Time Frame: 5 year
time from random assignment to first relapse (local, regional and distant), contralateral breast cancer
Secondary Outcomes
- distant disease-free survival(5 year)
- disease-free survival gBRCA1 mutation carriers and homologous recombination repair (HRR)-related gene mutation carriers(5 year)
- overall survival(5 year)
- relapse-free survival(5 year)