Clinical trial NCT03185871: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Carcinoma
Keywords: Invasive breast carcinoma
breast carcinoma stage T1cN0 to N3N0
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-06-14
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Changes in collagen
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Change in correlation of collagen alignment and COX-2 expression
timeFrame: Up to 6 weeks
measure: Changes in Syndecan-1
timeFrame: Up to 6 weeks
measure: Changes in CD68
timeFrame: Up to 6 weeks
measure: Changes in CD163
timeFrame: Up to 6 weeks
measure: Changes in neutrophil elastase
timeFrame: Up to 6 weeks
measure: Changes in vimentin
timeFrame: Up to 6 weeks
measure: Changes in α-SMA
timeFrame: Up to 6 weeks
measure: Changes in Ki67
timeFrame: Up to 6 weeks
measure: Changes in tissue cytokines in dense breast tissue
timeFrame: Up to 6 weeks
measure: Number of subjects with adverse events associated with celecoxib
timeFrame: Up to 6 weeks
measure: Changes in collagen due to relationship of amount/percentage of fibroglandular tissue
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of Wisconsin, Madison
name: Mark Burkard, MD
role: PRINCIPAL_INVESTIGATOR
References: