A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Change in cell surface expression of TRAIL receptor-2
研究概览
简要总结
Given preliminary data demonstrating that methionine deprivation enhances cell surface expression of TRAIL receptor-2, the objective of this clinical trial is to confirm that methionine restriction enhances its expression in triple negative breast cancer and to establish the feasibility and acceptability of this dietary intervention in humans. This study will also examine the effect of methionine restriction on cancer stem cells and metabolic health.
详细描述
Under the supervision of a registered dietitian, subjects will receive an individualized dietary prescription that incorporates a methionine-free amino acid-modified medical food (Hominex-2, Abbott Nutrition) supplemented with low-methionine foods. Hominex-2 contains a mixture of L-amino acids but lacks methionine. Subjects will be instructed in the preparation of Hominex-2 beverages (approximately 4-5 per day or per dietician recommendation) to deliver 100% of daily protein requirements (0.8 g/kg/day) and 40-45% of the caloric requirements. The remaining calories will be met with low-methionine foods, including fruits, vegetables, grains (e.g., specified cereal and bread), margarine and cooking oils. Subjects will be provided with a list of foods that are low in methionine. Calories will not be restricted. Subjects will be encouraged to follow their usual level of physical activity and instructed to maintain a daily diet and exercise diary that will be reviewed weekly by the dietitian.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Participants must have histologically confirmed operable triple negative breast cancer
- •ER (estrogen receptors) and PR (progesterone receptors) expression must be < 2%
- •HER2 must negative as shown be either 0 or 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR by a HER2: 17 centromere signal of <2.0 using a standard in situ hybridization method.
- •No prior therapy for current breast cancer
- •Operable breast cancer. Participants who are planned to undergo neo-adjuvant chemotherapy are eligible as long as they consent to an additional breast biopsy following the dietary intervention immediately prior to starting chemotherapy
- •ECOG (Eastern Cooperative Oncology Group) performance status ≤1
- •Ability to understand and the willingness to sign a written informed consent document
- •Serum creatinine <ULN (upper limit of normal)
- •Non-pregnant. Women of childbearing potential must have a negative pregnancy test to participate in this study
- •Women of childbearing potential must agree to use effective contraceptives (as discussed with their physician) while participating in this study
排除标准
- •Patients who are receiving any other investigational agents
- •Patients not able to swallow oral medications or with gastrointestinal conditions that may impact absorption of oral medications
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
结局指标
主要结局
Change in cell surface expression of TRAIL receptor-2
时间窗: Up to 3 weeks
To determine if methionine restriction can enhance the cell surface expression of TRAIL receptor-2 in triple negative breast cancers.
次要结局
- Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Up to 3 weeks)
- Effect of methionine restriction on cancer stem cell markers CD44 and CD24(Up to 3 weeks)
- Change in plasma concentrations(Up to 3 weeks)
- Change in subject weight(Up to 3 weeks)
- Change in subject BMI(Up to 3 weeks)
- Change in subject waist circumference(Up to 3 weeks)
- Change in subject metabolic indices(Up to 3 weeks)
- Change in body composition(Up to 3 weeks)