A Phase II, Randomized, Open Label Trial of Pre-operative (Neoadjuvant)Letrozole (Femara) vs. Letrozole in Combination With Avastin in Post Menopausal Women With Newly Diagnosed Operable Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 7
- 主要终点
- The Percentage of Participants With Pathologic Complete Response
研究概览
简要总结
This purpose of this trial is to show that the combination of Avastin and hormone therapy should be more effective than hormone therapy alone for the treatment of breast cancer.
详细描述
Preclinical and clinical data have demonstrated that up-regulation of tumor cell VEGF is an important mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced therapy response or tumor resistance to hormonal therapy; thus, it is hypothesized that the combination of an anti-VEGF agent (Avastin, an anti-VEGF monoclonal antibody) and hormonal therapy should be more effective than hormonal therapy alone for the treatment of breast cancer.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must meet the following criteria to be eligible for study entry:
- •Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of the breast, T2-T3 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone receptors, and Her-2-neu negative. Patients with inflammatory breast cancer will not be included (T4d). Patients previously treated patients with no measurable disease or patients with metastatic disease will be excluded.
- •Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
- •Patients must be postmenopausal, defined as one of the following:
- •Patients > 50 years of age with no spontaneous menses for at least 12 months,
- •Bilateral oophorectomy
- •Be ambulatory (outpatient) and have an ECOG PS <
- •Patients must have measurable disease by mammogram and/or breast ultrasound (in special cases a dedicated breast MRI may be clinically indicated). The target lesion must not have been previously irradiated.
- •No prior chemotherapy.
- •Patients must have adequate organ and marrow function as defined as follows: absolute neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3, total bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, Transaminases (AST, ALT) may be up to 2 x institutional upper limit of normal. In addition < 1 gr of protein in 24 hr urine collection and urine protein/creatinine ratio < 1.
- •No life threatening parenchymal disease or rapidly progressing disease warranting cytotoxic chemotherapy.
- •Hypertension must be controlled (<150/100 mmHg).
- •Ejection Fraction > 50% by echocardiogram. (LVEF greater than 75% at baseline should be reviewed and/or the test repeated as it may be falsely elevated).
- •No history of thrombosis during the previous 12 months.
排除标准
- •Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this sponsor-investigator Bevacizumab cancer study.
- •Uncontrolled high blood pressure (>150/100 mmHg).
- •Unstable angina
- •New York Heart Association (NYHA) Grade III or greater congestive heart failure
- •History of myocardial infarction or unstable angina within 12 months
- •History of stroke or TIA within 12 months
- •Clinically significant peripheral vascular disease
- •History of a bleeding disorder
- •Presence of central nervous system or brain metastases
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
- •Minor surgical procedures (excluding fine needle aspirations or core biopsies) within 5 days prior to Day 0
- •Pregnant (positive pregnancy test) or lactating
- •Urine protein: creatinine ratio greater than or equal to 1.0 at screening or patients demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to study entry will not participate in the trial.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
- •Serious, non-healing wound, ulcer, or bone fracture
- •Unwilling or unable to comply with the protocol for the duration of the study.
- •Psychiatric illness/social situations that would limit compliance with study requirements.
- •History of another malignancy within the last five years except non-melanoma skin cancer and carcinoma in-situ of uterine cervix.
- •Patients with metastatic disease.
研究组 & 干预措施
Letrozole + Avastin
50 evaluable patients received the combination therapy of 2.5 gm daily oral Letrozole and Avastin 15 mg/kg IV every 3 weeks for 24 weeks.
干预措施: Letrozole; Avastin (Drug)
Letrozole alone
25 evaluable patients received daily oral 2.5 mg letrozole as a single agent
干预措施: Letrozole (Femara) (Other)
结局指标
主要结局
The Percentage of Participants With Pathologic Complete Response
时间窗: 24 weeks
Pathological complete response is defined as the absence of residual invasive tumor in the breast or axillary lymph nodes or if only residual ductal carcinoma in-situ was seen on review of the surgical specimen.
次要结局
- Letrozole +Avastin(24 weeks)
研究者
Lisle Nabell
Professor, Med-Hematology & Oncology
University of Alabama at Birmingham