Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Changes in collagen
研究概览
简要总结
The overall purpose of this study is to assess whether celecoxib can reduce the change in collagen alignment and inflammatory response in the tumor tissue of primary breast cancer patients with invasive breast carcinoma after 2 weeks of oral intake.
详细描述
Advances in early detection techniques and improvement in systemic treatment of early stage breast cancer have led to a small decline in overall breast cancer mortality in the last 20 years. New advances will require understanding of breast cancer biology at the molecular level. Inhibition of COX-2 and its analysis of effect in breast cancer tumor microenvironment provide one such fruitful therapeutic target. Tumor microenvironment is poorly understood in breast cancer research. Despite new drugs being developed to treat breast cancer and tested in clinical trials, it is rarely possible to assess how the drug is affecting the breast cancer cells at a molecular level. The use of collagen properties such as alignment and deposition will allow giving a faster diagnosis of breast cancer status and seeing how celecoxib with respect to collagen can change the tumor microenvironment in human tissue. This window trial provides a way to look at cancer and stromal cells before and after celecoxib intake to see if the drug is actively working. If we can do this before and after a patient has surgery, and see how the tumor microenvironment responds, then the physician could pick a better suited adjuvant treatment for this patient after surgical intervention that would improve their overall survival rate.
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
盲法说明
Due to the characteristics of the design of this clinical trial, the patient will not be blinded but the researcher completing analysis will be. The researcher will be handling deidentified patient samples and comparing whether there are changes of biological markers within the same patient before and after celecoxib intake. It is important that the researcher be as unbiased as possible when analyzing collagen alignment and amount of other breast cancer biological markers.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants must have biopsy proven invasive breast carcinoma stages T1cN0 to T3N0, ER or PR positive with tumors greater than 1cm without lymph node spread.
- •Participants must have a mammographic breast composition category (density) of c or d.
- •Participants must be willing to participate and provide signed informed consent.
- •Participants must have no immediate requirements for chemotherapy, radiotherapy or hormonal therapy.
- •Participants must be willing to discontinue any use of NSAIDs like aspirin or ibuprofen until the tumor is removed
- •Participants cannot be taking the following medications because of major pharmacokinetic interactions with celecoxib while being enrolled in the study: Abciximab, Argatroban, Bivalirudin, Cilostazol, Dabigatran, Etexilate, Dipyridamole, Fondaparinux, Heparin, Lepirudin, Pemetrexed, Protein C, Rivaroxaban, Sibutramine, Ticlopidine, Tirofiban, Vilazodone and Warfarin.
- •Participants should pass MRI screening questionnaire
排除标准
- •Prior history of cancer, neo-adjuvant chemotherapy and radiation therapy
- •No daily NSAIDs intake within the past 4 weeks. Intermittent non-daily NSAIDs is allowed under PI discretion.
- •Current or prior systemic use of corticosteroids in the past month.
- •Participants with history of hypertension, congestive heart failure, edema, stroke or other cardiac disease or condition.
- •Participants with type 2 diabetes, documented stomach ulcers and pulmonary embolism.
- •Participants with aspirin or other NSAIDs-induced asthma or hypersensitivity reaction, sulfonamide allergy
- •Participants who are currently pregnant
- •Participants with known human immunodeficiency virus (HIV) infection, hepatitis B carrier state or with clinical evidence of hepatitis B.
- •Participants who are not able to understand or provide written informed consent.
- •Participants with standard contraindications to non-contrast MRI will be excluded, including claustrophobia and metallic implants incompatible with MRI.
- •Participants whose girth exceeds the bore of the MRI scanner.
- •Participants requiring conscious sedation for MR imaging.
研究组 & 干预措施
Celecoxib
The participants will be scheduled for the two quantitative breast MRI exams. Following the first MRI exam, participants will start taking celecoxib 200mg twice a day with food. Subjects will take a minimum of 26 doses and no more than 32 doses of celecoxib during the study.
Participants will intake 200mg of celecoxib two times a day (400mg/day total) for 2 weeks after biopsy. Histologic tissue samples will be obtained for evaluation at time of biopsy of the tumor and at time of surgery removal of the tumor.
干预措施: Celecoxib (Drug)
结局指标
主要结局
Changes in collagen
时间窗: Up to 6 weeks
To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment.
次要结局
- Change in correlation of collagen alignment and COX-2 expression(Up to 6 weeks)
- Changes in Syndecan-1(Up to 6 weeks)
- Changes in CD68(Up to 6 weeks)
- Changes in CD163(Up to 6 weeks)
- Changes in neutrophil elastase(Up to 6 weeks)
- Changes in vimentin(Up to 6 weeks)
- Changes in α-SMA(Up to 6 weeks)
- Changes in Ki67(Up to 6 weeks)
- Changes in tissue cytokines in dense breast tissue(Up to 6 weeks)
- Number of subjects with adverse events associated with celecoxib(Up to 6 weeks)
- Changes in collagen due to relationship of amount/percentage of fibroglandular tissue(Up to 6 weeks)