A Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Effect of Vandetanib on Cellular Markers of Proliferation and Apoptosis in Invasive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Ki-67 Cells Observed 2 Weeks Post-treatment
研究概览
简要总结
The purpose of this project is to examine whether treatment with vandetanib has an effect on the tumor cells in breast cancer by examining tissue markers.
详细描述
The purpose of this research study is to test whether vandetanib has an effect on tumor growth markers. Vandetanib is not approved by the FDA for use in treating breast cancer. This study will compare vandetanib to a placebo.
The proposed study is designed to determine the change in Ki-67 expression on paired breast cancer samples obtained before and after treatment with vandetanib. Other tumor markers including RET, TUNEL and phosphorylation specific levels of ERK1/2, AKT and mTOR will also be assessed on the paired samples.
Those who have a core biopsy of the breast which demonstrates invasive breast cancer and requires surgical excision of the lesion will be eligible for inclusion in the study. The tyrosine kinase inhibitor, vandetanib 300 mg, will be given once a day for 7-14 days prior to surgery. Following surgery, tissue markers would be analyzed on each of the paired samples, allowing for rapid assessment of in vivo response to TKI treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with core breast biopsy that, on pathology review, demonstrates invasive breast cancer and are determined to need surgical excision of the lesion. All subtypes of invasive breast cancer will be enrolled. Core biopsy specimens of enrolled patients will be stained for RET by immunohistochemistry and scored, however, patients will not be excluded according to RET expression.
- •Female gender
- •Age >/= 18 years of age
- •ECOG performance status </= 2
- •Life expectancy of greater than 6 months
- •Ability and willingness to provide informed consent to participate in study
排除标准
- •Prolonged QT interval (QTc > 480 milliseconds) on screening EKG or congenital long QT syndrome
- •Any concomitant medications that are known to be associated with Torsades de Pointes or QT elongation (see appendix 2).
- •Hypertension not controlled by medical therapy (systolic BP greater than 160 millimeters of mercury [mmHg] or diastolic blood pressure great than 100 mmHg).
- •Patients taking metformin or digoxin.
- •History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
- •Significant cardiac event (e.g., myocardial infarction), superior vena cava syndrome, New York Heart Association (NYHA) classification of heart disease ≥2 within 12 weeks, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
- •Serum calcium or magnesium outside the institutional range of normal.
- •Serum Potassium < 4.0 mmol/L or above 5.0 mmol/L
- •Creatinine clearance < 50 ml/min
- •PT > 12 seconds or PTT > 31 seconds
- •Platelet count of < 100,000
- •Serum bilirubin greater than 1.5 mg/dl
- •Alanine aminotransferase (ALT) > 50 U/L, aspartate aminotransferase (AST) > 65 U/L, or alkaline phosphatase (ALP) > 250 U/L
- •Any cytotoxic treatments, such as neoadjuvant chemotherapy, planned before subsequent surgical procedure.
- •Previous exposure to Vandetanib
- •Previous enrollment or randomization in this study
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at UIHC).
- •Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
- •Patients who have received prior surgical site radiation.
- •Patients on CYP3A4 inhibitors or inducers (see appendix 1).
- •Inability to test core biopsy for study markers
- •Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential.)
研究组 & 干预措施
Vandetanib
Vandetanib, 300 mg, PO, q day for 7-14 days prior to surgery
干预措施: Vandetanib (Drug)
Placebo
Placebo, PO, q day for 7-14 days prior to surgery.
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change From Baseline in Ki-67 Cells Observed 2 Weeks Post-treatment
时间窗: 2 weeks
Pre- and post-treatment samples will be assessed by immunohistochemistry for positivity for Ki-67.
次要结局
- Percent Change From Baseline in TUNEL Observed 2 Weeks Post-treatment(2 weeks)
研究者
Ronald Weigel
Professor
University of Iowa