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NSAID Effects on Clinical and Imaging Breast Biomarkers

Primary Purpose

Inflammation, Cancer, Pain

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sulindac

About this trial

This is an interventional treatment trial for Inflammation focused on measuring breast cancer, breast density, chemoprevention

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

University of Arizona Cancer Center
Stony Brook University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Sulindac (Clinoril)

Observational

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01761877

First Posted

December 28, 2012

Last Updated

January 13, 2023

Sponsor

Stony Brook University

1. Study Identification

Unique Protocol Identification Number

NCT01761877

Brief Title

NSAID Effects on Clinical and Imaging Breast Biomarkers

Official Title

NSAID Effects on Clinical and Imaging Breast Biomarkers

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

February 7, 2019 (Actual)

Study Completion Date

March 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stony Brook University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammation, Cancer, Pain, Hypertension

Keywords

breast cancer, breast density, chemoprevention

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

114 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sulindac (Clinoril)

Arm Type

Experimental

Arm Description

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.

Arm Title

Observational

Arm Type

No Intervention

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Sulindac

Other Intervention Name(s)

Clinoril

Primary Outcome Measure Information:

Title

Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging

Description

Adjusted estimates of relative change in percent breast density by magnetic resonance imaging

Time Frame

Baseline and 12 months

Secondary Outcome Measure Information:

Title

Muscle and Joint Pain and Stiffness

Description

Time Frame

Baseline and 12 months

Other Pre-specified Outcome Measures:

Title

Change in Mean Arterial Blood Pressure at 12 Months

Description

Adjusted estimate of change in mean arterial blood pressure in each study arm at 12 months in each study arm.

Time Frame

Change in blood pressure between Baseline and 12 months

10. Eligibility

Sex

Female

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patricia Thompson-Carino, PhD

Organizational Affiliation

Stony Brook University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alison Stopeck, MD

Organizational Affiliation

Stony Brook University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Pavani Chalasani, MD

Organizational Affiliation

University of Arizona

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Arizona Cancer Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

Facility Name

Stony Brook University Cancer Center

City

Stony Brook

State/Province

New York

ZIP/Postal Code

11794

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

35039952

Citation

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.

Results Reference

derived

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NSAID Effects on Clinical and Imaging Breast Biomarkers

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