A Randomized Phase II Trial of Weekly Nanoparticle Albumin Bound Paclitaxel (Nab-Paclitaxel) (NSC-736631) With or Without Bevacizumab, Either Preceded by or Followed by Q 2 Week Doxorubicin (A)and Cyclophosphamide (C) Plus Pegfilgrastim (PEG-G) as Neoadjuvant Therapy For Inflammatory and Locally Advanced HER-2/NEU Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 215
- 试验地点
- 365
- 主要终点
- Number of Patients With Pathological Complete Response Rate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which treatment regimen is more effective in treating women with breast cancer.
PURPOSE: This randomized phase II trial is studying paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, cyclophosphamide, and pegfilgrastim to compare how well they work when given with or without bevacizumab in treating women with inflammatory or locally advanced breast cancer.
详细描述
OBJECTIVES:
- To compare the pathologic complete response rates in women with HER2/neu-negative inflammatory or locally advanced breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin hydrochloride, cyclophosphamide, and pegfilgrastim with vs without bevacizumab.
- To compare the overall survival of patients treated with these regimens.
- To assess whether there is a correlation between bevacizumab and stratification factors (type of disease and hormone receptor status).
- To compare the toxicities of these regimens.
- To explore the molecular biomarkers related to the biology and outcome of inflammatory breast cancer.
- To explore potential molecular biomarkers that predict response to therapy and drug sensitivity.
- To evaluate biomarkers with respect to the sequence of paclitaxel albumin-stabilized nanoparticle formulation and doxorubicin hydrochloride/cyclophosphamide/pegfilgrastim administration in patients not receiving bevacizumab.
- To explore residual cancer burden and correlate it with outcome.
- To evaluate the time to treatment failure prior to surgery.
- To evaluate disease-free survival from the time of surgery in patients undergoing definitive surgery.
OUTLINE: This is a multicenter study. Patients are stratified according to type of disease (inflammatory vs locally advanced breast cancer) and hormone receptor status (positive [estrogen receptor (ER)+ and/or progesterone receptor (PgR)+] vs negative [ER- and PgR-]). Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
- Arm II: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
- Arm III: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11. Patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.
In all arms, patients with stable or responding disease undergo surgery 3-6 weeks after completion of chemotherapy. Patients may then undergo radiotherapy 5 days a week for 6 weeks.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: bevacizumab (Biological)
Arm 1
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: pegfilgrastim (Biological)
Arm 1
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: cyclophosphamide (Drug)
Arm 1
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: doxorubicin hydrochloride (Drug)
Arm 1
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Arm 2
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12, and then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: pegfilgrastim (Biological)
Arm 2
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12, and then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: cyclophosphamide (Drug)
Arm 2
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12, and then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: doxorubicin hydrochloride (Drug)
Arm 2
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12, and then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Arm 3
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11, and then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.
干预措施: pegfilgrastim (Biological)
Arm 3
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11, and then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.
干预措施: cyclophosphamide (Drug)
Arm 3
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11, and then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.
干预措施: doxorubicin hydrochloride (Drug)
Arm 3
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11, and then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
结局指标
主要结局
Number of Patients With Pathological Complete Response Rate
时间窗: pre-study pathology vs. post-chemo surgery pathology (approx. 39-42 weeks post-randomization)
Pathologic complete response (pCR), commonly defined as the absence of residual invasive cancer in both the breast and axillary lymph nodes, has emerged as a surrogate endpoint for disease-free and overall survival, as the achievement of a pCR is associated with a favorable long-term prognosis in all breast cancer subtypes.
次要结局
- Overall Survival(Disease assessed every 4 weeks while on treatment then every 6 months for one year then annually for four years from registration.)
- Event-free Survival(Disease assessed every 4 weeks while on treatment then every 6 months for one year then annually for four years from registration or until recurrence)
- Number of Adverse Events That Are Possibly, Probably or Definitely Related to Study Drug(Up to 28 weeks)