Back to resultsCelecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
Primary Purpose
Breast Carcinoma
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Celecoxib
Sponsored by
About this trial
This is an interventional basic science trial for Breast Carcinoma focused on measuring Invasive breast carcinoma, breast carcinoma stage T1cN0 to N3N0
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Celecoxib
Arm Description
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.
Outcomes
Primary Outcome Measures
Changes in collagen
To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment.
Secondary Outcome Measures
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.
Changes in Syndecan-1
To analyze Syndecan-1 expression levels as stromal response biomarkers.
Changes in CD68
To analyze CD68 expression levels as stromal response biomarkers.
Changes in CD163
To analyze CD163 expression levels as stromal response biomarkers.
Changes in neutrophil elastase
To analyze neutrophil elastase expression levels as stromal response biomarkers.
Changes in vimentin
To analyze vimentin expression levels as stromal response biomarkers.
Changes in α-SMA
To analyze α-SMA expression levels as stromal response biomarkers.
Changes in Ki67
To analyze Ki67 expression levels as stromal response biomarkers.
Changes in tissue cytokines in dense breast tissue
To discover tissue cytokines present in dense breast tissue that are altered in response to celecoxib.
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.
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.
Full Information
NCT ID
NCT03185871
First Posted
June 9, 2017
Last Updated
November 13, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03185871
Brief Title
Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
Official Title
Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Slow accrual
Study Start Date
September 20, 2017 (Actual)
Primary Completion Date
October 10, 2018 (Actual)
Study Completion Date
October 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma
Keywords
Invasive breast carcinoma, breast carcinoma stage T1cN0 to N3N0
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
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.
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Celecoxib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in collagen
Description
To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment.
Time Frame
Up to 6 weeks
Secondary Outcome Measure Information:
Title
Change in correlation of collagen alignment and COX-2 expression
Description
To evaluate correlation among collagen alignment and COX-2 expression before and after celecoxib intake.
Time Frame
Up to 6 weeks
Title
Changes in Syndecan-1
Description
To analyze Syndecan-1 expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in CD68
Description
To analyze CD68 expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in CD163
Description
To analyze CD163 expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in neutrophil elastase
Description
To analyze neutrophil elastase expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in vimentin
Description
To analyze vimentin expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in α-SMA
Description
To analyze α-SMA expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in Ki67
Description
To analyze Ki67 expression levels as stromal response biomarkers.
Time Frame
Up to 6 weeks
Title
Changes in tissue cytokines in dense breast tissue
Description
To discover tissue cytokines present in dense breast tissue that are altered in response to celecoxib.
Time Frame
Up to 6 weeks
Title
Number of subjects with adverse events associated with celecoxib
Description
To evaluate any adverse events associated with the 2-week intake of 200mg celecoxib twice a day.
Time Frame
Up to 6 weeks
Title
Changes in collagen due to relationship of amount/percentage of fibroglandular tissue
Description
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.
Time Frame
Up to 6 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Burkard, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
12. IPD Sharing Statement
Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center Homepage
Learn more about this trial
Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
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