A Multicenter, Placebo-Controlled, Double-Blind Randomized Phase II Trial of Neoadjuvant Treatment With Single-Agent Bevacizumab or Placebo, Followed by Six Cycles of Docetaxel, Doxorubicin, and Cyclophosphamide (TAC), With or Without Bevacizumab in Patients With Stage II or Stage III Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 9
- 主要终点
- •To evaluate the safety and toxicity of the TAC regimen with the addition of bevacizumab given as preoperative therapy to patients with Stage II or Stage III breast cancer
研究概览
简要总结
The purpose of this study is to evaluate the safety of the TAC-bevacizumab combination and investigate whether changes in gene expression, or the expression of specific biomarkers, are either predictive of response to bevacizumab or indicative of response.
详细描述
The study combines bevacizumab with a very efficacious combination chemotherapy regimen for the treatment of stage II or stage III primary breast cancer. Safety of the TAC-bevacizumab combination will be evaluated. In addition, the study design incorporates an initial cycle of bevacizumab or placebo alone. Assessing the isolated effects of bevacizumab in a setting where pre- and post-treatment tissue specimens can be obtained will provide essential information about the mechanisms by which VEGF inhibition affects tumor growth, and represents an ideal opportunity to evaluate the molecular effects of bevacizumab on breast tumor tissue.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven adenocarcinoma of the breast
- •Stage II (T > 3 cm) or Stage III disease (except inflammatory breast cancer), according to the AJCC Staging Manual, 6th Edition, 2002
- •HER2-negative disease (as defined by fluorescence in situ hybridization [FISH])
- •ECOG performance status 0-1
- •No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or noninvasive breast cancer
- •Normal cardiac function (ejection fraction > lower limit of normal) as determined by MUGA or echocardiogram
- •Adequate organ function
排除标准
- •Prior chemotherapy or radiotherapy for Stage II or Stage III breast cancer
- •Inflammatory Breast Cancer, clinically defined as the presence of erythema or induration involving one-third or more of the breast
- •Prior treatment with an anti-angiogenic agent
- •Prior ipsilateral radiation therapy for invasive or non-invasive breast cancer
- •Bilateral invasive breast cancer
- •Concurrent therapy with any other non-protocol anti-cancer therapy
- •Current therapy with hormone replacement therapy, or any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (agents must be stopped prior to randomization)
- •Presence of neuropathy > grade 2 (NCI-CTC version 3.0) at baseline
- •Presence of any non-healing wound, bone fracture, or ulcer, or the presence of clinically significant (> grade 2) peripheral vascular disease
- •History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix
- •Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100], myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- •Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning therapy
- •Active, uncontrolled infection requiring parenteral antimicrobials
- •The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications
- •Pregnancy or lactation
- •A history of a severe hypersensitivity reaction to bevacizumab, or docetaxel or other drugs formulated with polysorbate 80
- •Evidence of bleeding diathesis or coagulopathy
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration, or core biopsy within 7 days prior to beginning therapy
- •Urine protein:creatinine ratio of > 1.0 at screening
研究组 & 干预措施
Bevacizumab 7.5 and TAC
one dose of Bevacizumab (7.5mg/kg) will be administered intravenously every 3 weeks followed by TAC.
干预措施: Bevacizumab 7.5 and TAC (Drug)
Placebo 7.5 and TAC
Placebo7.5 will be administered intravenously every 3 weeks followed by TAC.
干预措施: Placebo 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) (Drug)
Bevacizumab 15 and TAC
one dose of Bevacizumab (15mg/kg) will be administered intravenously every 3 weeks followed by TAC.
干预措施: Bevacizumab 15 and TAC (Drug)
Placebo 15 and TAC
Placebo 15mg/kg will be administered intravenously every 3 weeks followed by TAC.
干预措施: Placebo 15 and TAC (Drug)
结局指标
主要结局
•To evaluate the safety and toxicity of the TAC regimen with the addition of bevacizumab given as preoperative therapy to patients with Stage II or Stage III breast cancer
时间窗: 4 years
Patients will be evaluated for adverse events (all grades) at each study visit for the duration of their participation in the study. All AEs should be graded using the NCI--CTCAE, Version 3.0. Patients discontinued from the treatment phase of the study for any reason will be evaluated within 30 days after the decision to discontinue treatment.
•To estimate change from baseline expression of HIF1α as a measure of tumor angiogenesis, after a single dose of bevacizumab as compared to placebo
时间窗: 4 years
次要结局
- •To estimate the rate of post-surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab(4 years)
- •To estimate the rate of CHF in patients receiving TAC with or without bevacizumab(4 years)
- •To estimate the rates of left ventricular ejection fraction (LVEF) changes as measured by either a decrease of > 15% from baseline, or > 10% to a value below the lower limit of normal (for the institution), in patients receiving TAC or TAC + bevacizumab(4 years)
- •To investigate the clinical efficacy of TAC and TAC plus bevacizumab by estimating the clinical objective response rate (CR + PR), pathologic complete response rate (pCR), and rate of breast-conserving surgery (BCS)(4 years)