Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
研究概览
简要总结
This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo.
II. Determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib at 1000 mg as compared to women taking placebo.
SECONDARY OBJECTIVES:
I. Determine whether lapatinib treatment affects the incidence of DCIS seen at the time of surgical excision.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants must be premenopausal or postmenopausal
- •Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy
- •The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)
- •All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- •Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1
- •If subjects are of reproductive potential, they must agree to use a reliable contraceptive method or be sexually abstinent; subjects must fulfill these conditions beginning at the time of starting study medications and ending one month after study termination
- •Negative serum pregnancy test (beta-human chorionic gonadotropin [HCG]) at baseline (within 30 days of day 0) for women of child bearing potential
- •Serum creatinine =< 1.5 times the institution?s upper limit of normal
- •Total bilirubin =< 1.5 times the institution's upper limits of normal
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 times the institution's upper limits of normal
- •Alkaline phosphatase =< 1.5 times the institution's upper limits of normal
- •Albumin =< 1.5 times the institution's upper limits of normal
- •White blood cells (WBC) > 4.0 k/uL
- •Platelet count > 100,000/uL
- •Hematocrit of > 30%
- •Cardiac ejection fraction within normal limits for the institution by multi gated acquisition scan (MUGA) scan or normal cardiac ultrasound (defined as within the upper limit of normal [ULN] for the institution)
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Willingness to refrain from donating blood to others during the study
排除标准
- •Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years
- •Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)
- •Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1
- •Individuals currently receiving anticoagulation therapy (e.g., Coumadin) are ineligible
- •Blood urea nitrogen [BUN] > 1.5 x ULN or
- •Creatinine [Cr] > 1.5 x ULN
- •SGOT > 1.5 x ULN
- •Serum glutamate pyruvate transaminase (SGPT) > 1.5 x ULN
- •Alkaline phosphatase > 1.5 x ULN
- •Bilirubin > 1.5x ULN
- •Individuals who are currently participating in a study of an investigational drug
- •Pregnancy, lactation or unwillingness to use a reliable contraceptive method in women of childbearing potential
- •Severe underlying chronic illness or disease, such as uncontrolled diabetes
- •Individuals with known congestive heart disease or previous myocardial infarction are ineligible
- •Patients taking any prohibited medications
- •Individuals with hypokalemia or hypomagnesemia are ineligible unless these conditions are corrected to within normal limits before starting drug
- •Individuals with congenital long QT syndrome or baseline QTcF intervals > 480 msec on electrocardiogram (EKG)
- •Individuals taking anti-arrhythmics, beta blockers, or other medications that may lead to QT prolongation
- •Individuals who have received a cumulative dose of anthracycline therapy greater than 500 mg/m^2 are ineligible
研究组 & 干预措施
Arm I (lapatinib ditosylate)
Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (lapatinib ditosylate)
Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.
干预措施: Lapatinib Ditosylate (Drug)
Arm II (placebo)
Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
时间窗: From baseline to 4-5 weeks after surgery
Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
时间窗: 2-6 weeks from baseline to surgery, up to 6 weeks
Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.
次要结局
- Biomarker Analysis of Proliferation Markers(2-6 weeks from baseline to surgery, Up to 6 weeks)
- Incidence of Ductal Carcinoma in Situ Remaining at Resection(2-6 weeks from baseline to surgery, up to 6 weeks)