Clinical Trials /

Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses

NCT03185871

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: UW16141
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: 2017-0219
  • NCT ID: NCT03185871

Conditions

  • Breast Carcinoma

Interventions

DrugSynonymsArms
CelecoxibCelebrexCelecoxib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
CelecoxibExperimentalThe 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.
  • Celecoxib

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.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Trial Keywords

  • Invasive breast carcinoma
  • breast carcinoma stage T1cN0 to N3N0

Last Updated

December 12, 2017