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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 : Recruiting
First Posted : June 14, 2017
Last Update Posted : December 14, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

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.

Condition or disease Intervention/treatment Phase
Breast Carcinoma Drug: Celecoxib Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
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
Official Title: Celecoxib Window of Opportunity Trial to Assess Tumor and Stroma Responses
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Celecoxib

Arm Intervention/treatment
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.

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Changes in Syndecan-1 [ Time Frame: Up to 6 weeks ]
    To analyze Syndecan-1 expression levels as stromal response biomarkers.

  3. Changes in CD68 [ Time Frame: Up to 6 weeks ]
    To analyze CD68 expression levels as stromal response biomarkers.

  4. Changes in CD163 [ Time Frame: Up to 6 weeks ]
    To analyze CD163 expression levels as stromal response biomarkers.

  5. Changes in neutrophil elastase [ Time Frame: Up to 6 weeks ]
    To analyze neutrophil elastase expression levels as stromal response biomarkers.

  6. Changes in vimentin [ Time Frame: Up to 6 weeks ]
    To analyze vimentin expression levels as stromal response biomarkers.

  7. Changes in α-SMA [ Time Frame: Up to 6 weeks ]
    To analyze α-SMA expression levels as stromal response biomarkers.

  8. Changes in Ki67 [ Time Frame: Up to 6 weeks ]
    To analyze Ki67 expression levels as stromal response biomarkers.

  9. 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.

  10. 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.

  11. 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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03185871


Contacts
Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Locations
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cancer Connect    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Principal Investigator: Mark Burkard, MD, PhD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Burkard, MD University of Wisconsin, Madison

Additional Information:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03185871     History of Changes
Other Study ID Numbers: UW16141
P30CA014520 ( U.S. NIH Grant/Contract )
2017-0219 ( Other Identifier: Institutional Review Board )
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: December 14, 2017
Last Verified: December 2017

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

Keywords provided by University of Wisconsin, Madison:
Invasive breast carcinoma
breast carcinoma stage T1cN0 to N3N0

Additional relevant MeSH terms:
Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents