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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 647
- 主要终点
- disease-free survival
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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;
- •WHO Performance status (ECOG) of 0 or 1;
- •Adequate recovery from recent surgery (at least one week must have elapsed from the time of a minor surgery (excluding breast biopsy); at least three weeks for major surgery);
- •Adequate hematological function (neutrophil count ³ 2x109/l, platelet count ³ 100x 109/l, Hemoglobin > 9 g/dl);
- •Adequate hepatic function: ASAT and ALAT ≤ 3 ULN alkaline phosphatases ≤ 2.5 ULN,total bilirubin ≤ 1,5 ULN;
- •Adequate renal function: serum creatinine ≤ 1 ULN;
- •Patients accepting contraception intake during the overall length of treatment if of childbearing potential;
- •Adequate cardiac function, LEVF value > 50% by Muga scan or echocardiography;
- •Signed written informed consent.
排除标准
- •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);
- •Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension (>150/90), myocardial infarction or cerebral vascular accidents) within 6 months prior to randomization;
- •Known prior severe hypersensitivity reactions to agents containing Cremophor EL;
- •Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 8 weeks after treatment completion;
- •Women who are pregnant or breastfeeding. Adequate birth control measures should be taken during study treatment phase;
- •Women with a positive pregnancy test en enrollment or prior to study drug administration;
- •Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
- •Individual deprived of liberty or placed under the authority of a tutor.
研究组 & 干预措施
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
干预措施: Paclitaxel Cisplatin (Drug)
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
干预措施: fluorouracil epirubicin cyclophosphamide and docetaxel (FEC-T) (Drug)
结局指标
主要结局
disease-free survival
时间窗: 5 year
time from random assignment to first relapse (local, regional and distant), contralateral breast cancer
次要结局
- 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)