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Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses

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ClinicalTrials.gov Identifier: NCT03185871
Recruitment Status : Withdrawn (Slow accrual)
First Posted : June 14, 2017
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE June 9, 2017
First Posted Date  ICMJE June 14, 2017
Last Update Posted Date October 16, 2018
Actual Study Start Date  ICMJE September 20, 2017
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
Changes in collagen [ Time Frame: Up to 6 weeks ]
To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03185871 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
  • Change in correlation of collagen alignment and COX-2 expression [ Time Frame: Up to 6 weeks ]
    To evaluate correlation among collagen alignment and COX-2 expression before and after celecoxib intake.
  • Changes in Syndecan-1 [ Time Frame: Up to 6 weeks ]
    To analyze Syndecan-1 expression levels as stromal response biomarkers.
  • Changes in CD68 [ Time Frame: Up to 6 weeks ]
    To analyze CD68 expression levels as stromal response biomarkers.
  • Changes in CD163 [ Time Frame: Up to 6 weeks ]
    To analyze CD163 expression levels as stromal response biomarkers.
  • Changes in neutrophil elastase [ Time Frame: Up to 6 weeks ]
    To analyze neutrophil elastase expression levels as stromal response biomarkers.
  • Changes in vimentin [ Time Frame: Up to 6 weeks ]
    To analyze vimentin expression levels as stromal response biomarkers.
  • Changes in α-SMA [ Time Frame: Up to 6 weeks ]
    To analyze α-SMA expression levels as stromal response biomarkers.
  • Changes in Ki67 [ Time Frame: Up to 6 weeks ]
    To analyze Ki67 expression levels as stromal response biomarkers.
  • Changes in tissue cytokines in dense breast tissue [ Time Frame: Up to 6 weeks ]
    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 [ Time Frame: Up to 6 weeks ]
    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 [ Time Frame: Up to 6 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
Official Title  ICMJE Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention 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.
Primary Purpose: Basic Science
Condition  ICMJE Breast Carcinoma
Intervention  ICMJE Drug: Celecoxib
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.
Other Name: Celebrex
Study Arms  ICMJE Experimental: 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.

Intervention: Drug: Celecoxib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 11, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2017)
45
Actual Study Completion Date  ICMJE October 10, 2018
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT03185871
Other Study ID Numbers  ICMJE UW16141
P30CA014520 ( U.S. NIH Grant/Contract )
2017-0219 ( Other Identifier: Institutional Review Board )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Mark Burkard, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP