Phase II Feasibility Trial Incorporating Bevacizumab Into Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Patients With Lymph Node Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 226
- 试验地点
- 1
- 主要终点
- Congestive Heart Failure Rate
研究概览
简要总结
This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works in treating patients who have undergone surgery for breast cancer that has spread to the lymph nodes. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with more than one chemotherapy drug (combination chemotherapy), may be a better way to block tumor growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the incidence of clinically apparent cardiac dysfunction in patients with lymph node positive breast cancer treated with bevacizumab and dose dense doxorubicin/cyclophosphamide followed by paclitaxel (ddAC > T).
SECONDARY OBJECTIVES:
I. To evaluate changes in LVEF during treatment. II. To evaluate non-cardiac toxicity.
OUTLINE: This is a non-randomized, multicenter study. Patients are sequentially assigned to 1 of 2 treatment arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the breast with involvement of at least one axillary or internal mammary lymph node on routine histologic examination with hematoxylin and eosin staining; NOTE: patients with axillary or internal mammary node involvement only demonstrated by immunohistochemistry are not eligible
- •Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, lumpectomy and axillary dissection, or lumpectomy and sentinel node biopsy; NOTE: axillary dissection is strongly encouraged in patients with lymph node involvement identified on sentinel node biopsy
- •Margins of lumpectomy or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible
- •(ARM A ONLY) Interval between last surgery for breast cancer (lumpectomy, mastectomy, sentinel node biopsy, axillary dissection or re-excision of lumpectomy margins) and D1 must be > 28 days and =< 84 days
- •ECOG performance status of 0-2
- •Absolute neutrophil count >= 1000/mm^3
- •Platelet count >= 100,000/mm^3
- •Total bilirubin =< 1.5 mg/dL
- •AST =< 2 upper limit of normal
- •Serum creatinine =< 1.5 mg/dL
- •Urine protein: creatinine ratio < 1.0
- •PT INR =< 1.5
- •PTT =< 1.5 x normal
- •LVEF >= institutional limits of normal by MUGA or ECHO
- •Prior to registration the investigator must specify if radiation is planned; patients who have undergone a lumpectomy must receive radiation; post-mastectomy radiation is at the investigator's discretion
- •Patients with HER2+ (3+ by IHC or FISH+) breast cancer are not eligible and should be treated with a trastuzumab-based adjuvant therapy
- •Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher TMN stage tumor meets the eligibility criteria for this trial
- •Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes (N2) at diagnosis
- •Patients must not have received prior cytotoxic chemotherapy, hormonal therapy or radiation for this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed; NOTE: prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry; similarly prior raloxifene use is allowed but must be discontinued at study entry
- •Patients must not have had a major surgical procedure within 4 weeks of entry; NOTE: non-operative biopsy or placement of a vascular access device is not considered a major surgery
- •Patients must not have clinically significant cardiovascular disease including:
- •New York Heart Association (NYHA) grade II or greater congestive heart failure
- •Grade II or greater peripheral vascular disease
- •Uncontrolled hypertension defined as SBP > 160 or DBP > 90
- •Any prior history of cerebrovascular disease including TIA or stroke
- •Patients must not require therapeutic anticoagulation; patients with a history of deep venous thrombosis or pulmonary embolism are not eligible; NOTE: prophylactic use of anticoagulants to maintain patency of a vascular assess device is permitted
- •Patients may not require regular use of aspirin (daily for >= 10 days at doses of > 325 mg/day) or regular therapeutic doses of other nonsteroidal anti-inflammatory agents known to inhibit platelet function; additionally, patients using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal); NOTE: regular use of Cox-2 inhibitors is permitted; NOTE: low-dose aspirin is permitted
- •Patients must not have a non-healing wound or fracture; patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months are excluded
- •Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
- •Patients who have experienced myocardial infarction or unstable angina within 12 months are excluded
- •Patients who have had experienced an arterial thrombotic event within 12 months are excluded
- •Patients must not have uncontrolled or clinical significant arrhythmia
- •Women must not be pregnant or breast-feeding due to the potential harmful effects of bevacizumab on the developing fetus; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- •Women of childbearing potential and sexually active males are required to use an accepted and effective method of contraception while on study and for at least 3-4 months after the last dose of bevacizumab
排除标准
- 未提供
研究组 & 干预措施
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: doxorubicin hydrochloride (Drug)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: cyclophosphamide (Drug)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: bevacizumab (Biological)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: paclitaxel (Drug)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: filgrastim (Biological)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: pegfilgrastim (Biological)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: radiation therapy (Radiation)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: tamoxifen citrate (Drug)
Arm I (combination chemotherapy, 18 courses of bevacizumab)
See detailed description.
干预措施: aromatase inhibition therapy (Drug)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: doxorubicin hydrochloride (Drug)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: cyclophosphamide (Drug)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: bevacizumab (Biological)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: paclitaxel (Drug)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: filgrastim (Biological)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: pegfilgrastim (Biological)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: radiation therapy (Radiation)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: tamoxifen citrate (Drug)
Arm II (combination chemotherapy, 22 courses of bevacizumab)
See detailed description.
干预措施: aromatase inhibition therapy (Drug)
结局指标
主要结局
Congestive Heart Failure Rate
时间窗: assessed on day 1 of cycles 5, 9, 17 and 25, and at end of treatment, then every 3 months for <2 years and every 6 months for 2-3 years from study entry
Clinical congestive heart failure includes patients with symptomatic decline in LVEF to at or below the lower limit of normal (LLN), or symptomatic diastolic dysfunction. 223 treated patients were included in the analysis.
次要结局
- Proportion of Patients With Absolute Decrease in Left Ventricular Ejection Fraction (LVEF) Levels Post Doxorubicin and Cyclophosphamide(AC)(assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment)
- Proportion of Patients With Absolute Decrease in LVEF Levels Post Bevacizumab(assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment)