NSAID Effects on Clinical and Imaging Breast Biomarkers

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.

Study Overview

• Status: Completed
• Conditions: Pain; Inflammation; Hypertension; Cancer
• Intervention / Treatment: Drug: Sulindac

Detailed Description

To accomplish our study aims, we will conduct a phase II, single are trial of sulindac in postmenopausal women with early stage ER+ breast cancer who are receiving an aromatase inhibitor as adjuvant hormonal therapy. Approximately 75 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, 6 and 12 months.

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 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 in general pain and joint specific stiffness and pain as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). 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. Tissue studies will include characterization of tissue histology (graded by cellularity and stromal elements) and molecular measures of proliferation and apoptosis.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Sulindac; Other Names: Clinoril
NO_INTERVENTION: Observational; Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their treatment will be monitored with MRI and standard of care tests every 6 months for up to 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging	Adjusted estimates of relative change in percent breast density by magnetic resonance imaging	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle and Joint Pain and Stiffness	The endpoint for arthralgia is change from baseline in Total Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index scores on a scale at 12 months. The Western Ontario and McMaster Universities Index is a self-administered questionnaire consisting of 24 items divided in 3 subscales: Pain, Stiffness, and Physical Function. Scores on the scale range from 0 to 96 for total WOMAC where 0 represents the best health status and 96 the worst possible status.	Baseline and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Arterial Blood Pressure at 12 Months	Adjusted estimate of change in mean arterial blood pressure in each study arm at 12 months in each study arm.	Change in blood pressure between Baseline and 12 months

Collaborators and Investigators

• Sponsor: Stony Brook University

Publications and helpful links

General Publications

• Martinez JA, Wertheim BC, Roe DJ, Chalasani P, Cohen J, Baer L, Chow HS, Stopeck AT, Thompson PA. Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. Breast Cancer Res Treat. 2022 Feb;192(1):113-122. doi: 10.1007/s10549-021-06485-0. Epub 2022 Jan 18.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): February 7, 2019
• Study Completion (ACTUAL): March 11, 2019

Study Registration Dates

• First Submitted: December 28, 2012
• First Submitted That Met QC Criteria: January 3, 2013
• First Posted (ESTIMATE): January 7, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer, breast density, chemoprevention
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Sulindac
• Other Study ID Numbers: 1RO1 CA1615301A1; 12-0080-04 (OTHER: UArizona); 676847 (OTHER: Stony Brook University)

Drug and device information, study documents

• 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