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NSAID Effects on Clinical and Imaging Breast Biomarkers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01761877
Recruitment Status : Active, not recruiting
First Posted : January 7, 2013
Last Update Posted : November 30, 2018
Information provided by (Responsible Party):
Alison Stopeck, Stony Brook University

Tracking Information
First Submitted Date  ICMJE December 28, 2012
First Posted Date  ICMJE January 7, 2013
Last Update Posted Date November 30, 2018
Study Start Date  ICMJE December 2012
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
Change in breast density measured as fat to water ratio by magnetic resonance imaging [ Time Frame: Baseline and 16 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01761877 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
Muscle and joint pain and stiffness [ Time Frame: Baseline and 16 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 3, 2013)
Clinically significant change in blood pressure [ Time Frame: Baseline and 16 months ]
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE NSAID Effects on Clinical and Imaging Breast Biomarkers
Official Title  ICMJE NSAID Effects on Clinical and Imaging Breast Biomarkers
Brief Summary This study has two purposes. One is to determine if daily sulindac decreases breast density; a risk factor for breast cancer development. The second is to determine whether sulindac reduces pain and stiffness associated with regular use of aromatase inhibitors given for the treatment of breast cancer.
Detailed Description

To accomplish our study aims, we will conduct a non-randomized phase II trial of AI alone as anastrozole in combination with sulindac in postmenopausal women with early stage ER+ breast cancer who are receiving an anastrozole as their adjuvant hormonal therapy. Recruitment will be limited to women on anastrozole to reduce heterogeneity introduced by other AIs. Anastrozole is selected as it is the only AI available in generic form and currently comprises almost 100% of our patient population. Approximately 100 breast cancer patients, stable on AI therapy (minimum of 3 months) for the treatment of their breast cancer will receive sulindac 150 mg bid for 12 months. Breast imaging will be conducted at baseline, 3, 9 and 15 months. A one-month run-in period followed by a 3-month observation, no agent period will be used to identify subjects likely not to adhere to the study regimen and to determine the extent of variability in breast density over time.

The primary endpoint of the study will be change in the appearance of the contralateral, uninvolved breast as measured by quantitative Fat Water Ratio (FWR-MRI) mapping at 12 months in response to either control (anastrozole alone) or experimental (anastrozole + sulindac) therapy. As changes in breast density in the contralateral, uninvolved breast will be the primary endpoint of the study, patients with bilateral breast cancer or those patients undergoing bilateral mastectomies or reconstruction surgery will be ineligible. Secondary endpoints of the trial include 12 month change between arms in diffusion weighted MRI (median ADC value) and general pain and joint specific stiffness and pain as assessed by the BPI-SF. A number of exploratory endpoints are planned and include comparison of MRI measures of the breast, tissue biomarkers, and pain at 6 months as early indicators of 12 month responses. For the tissue biomarkers, core needle biopsies will be obtained in a subset of women who consent to the procedure from the uninvolved contralateral breast at baseline and at 6 months. This is anticipated to be ~75% at baseline (n=100) (provides tissue sample for cross sectional comparative analyses with MRI features at baseline) and ~25% at 6 month follow-up visit (n=37) (provides tissue to conduct analyses of biomarker response to intervention). Tissue studies will include characterization of tissue histology (graded by cellularity and stromal elements) and molecular measures of proliferation and apoptosis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Inflammation
  • Cancer
  • Pain
  • Hypertension
Intervention  ICMJE Drug: Sulindac
Other Name: Clinoril
Study Arms  ICMJE
  • Experimental: Sulindac (Clinoril)
    Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will receive 150 mg of sulindac twice daily for 12 months. They will receive up to 4 MRI within 12 months.
    Intervention: Drug: Sulindac
  • No Intervention: Observational
    Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their treatment, and will be monitored with MRI and standard of care tests every 6 months for up to 12 months.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 28, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: January 3, 2013)
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligibility criteria will include: Postmenopausal women with of first incidence of early stage (stages 0 - III) hormone receptor positive breast cancer stabilized on anastrozole therapy for at least 3 months
  • Patients must have started on anastrozole and plan to continue on anastrozole therapy for a minimum of 12 months
  • Patients must have an unaffected, non-irradiated contralateral breast with a baseline breast density score of > 25% as measured by standard digital mammography (BIRADs score > 2) or magnetic resonance imaging (MRI) performed within 12 months of randomization to the study
  • A willingness to follow the study protocol, as indicated by provision of informed consent to participate
  • A willingness to avoid taking NSAIDs outside of the trial (rare NSAID use for musculoskeletal symptoms excepted)
  • Normal renal function as determined by a serum creatinine < upper limit of normal
  • No known contraindication to NSAID use
  • Normotensive or controlled blood pressure (< 140/90) on a single anti-hypertensive medication

Exclusion Criteria:

  • Current or anticipated need for daily aspirin or NSAID use including aspirin for cardiovascular protection
  • Known intolerance to NSAIDs
  • Age > 75 years
  • History of cardiovascular disease including prior myocardial infarction, angina, stroke, or transient ischemic attack (TIA)
  • Diabetes requiring drug therapy
  • Current smoker
  • History of Uncontrolled hypertension
  • Blood pressure > 140/90 at baseline by home monitoring
  • History of GI ulcers, chronic GERD, or GI bleeding in the past 5 years
  • History of a bleeding diathesis or current anticoagulant therapy
  • Daily therapy with H2 blockers or protein pump inhibitors
  • History of claustrophobia
  • Have electrically, magnetically, or mechanically activated implants including cardiac pacemaker, cochlear implants, magnetic surgical clips or prostheses.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE up to 75 Years   (Child, 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 United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01761877
Other Study ID Numbers  ICMJE 1RO1 CA1615301A1
12-0080-04 ( Other Identifier: UArizona )
676847 ( Other Identifier: Stony Brook University )
Has Data Monitoring Committee Yes
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.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alison Stopeck, Stony Brook University
Study Sponsor  ICMJE Stony Brook University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Patricia Thompson-Carino, PhD Stony Brook University
Principal Investigator: Alison Stopeck, MD Stony Brook University
Principal Investigator: Pavani Chalasani, MD University of Arizona
PRS Account Stony Brook University
Verification Date November 2018

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