Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses

Conditions
-----------------
Breast Carcinoma

Intervention / Treatment
-----------------
* Drug: Celecoxib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib<br>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. | Drug: Celecoxib<br>* Celecoxib is the only COX-2 inhibitor currently approved by the FDA to be used in the United States. Recently, it has been shown that celecoxib prevents sporadic colorectal adenomas and there are more clinical trials evaluating the use of celecoxib in combination with chemotherapy regimens in breast cancer settings. Celebrex® oral capsules that will be used in this study contain 200 mg of celecoxib, in combination with inactive ingredients that include the following components: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate.<br>* Other names: Celebrex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in collagen | To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in correlation of collagen alignment and COX-2 expression | To evaluate correlation among collagen alignment and COX-2 expression before and after celecoxib intake. | Up to 6 weeks | 
| Changes in Syndecan-1 | To analyze Syndecan-1 expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in CD68 | To analyze CD68 expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in CD163 | To analyze CD163 expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in neutrophil elastase | To analyze neutrophil elastase expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in vimentin | To analyze vimentin expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in α-SMA | To analyze α-SMA expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in Ki67 | To analyze Ki67 expression levels as stromal response biomarkers. | Up to 6 weeks | 
| Changes in tissue cytokines in dense breast tissue | To discover tissue cytokines present in dense breast tissue that are altered in response to celecoxib. | Up to 6 weeks | 
| Number of subjects with adverse events associated with celecoxib | To evaluate any adverse events associated with the 2-week intake of 200mg celecoxib twice a day. | Up to 6 weeks | 
| Changes in collagen due to relationship of amount/percentage of fibroglandular tissue | To determine if changes in collagen structure and proliferation in response to celecoxib differ by the amount and/or percentage of fibroglandular tissue, measured quantitatively using MRI. | Up to 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Invasive breast carcinoma, breast carcinoma stage T1cN0 to N3N0