NSAID Effects on Clinical and Imaging Breast Biomarkers

• ClinicalTrials.gov Identifier: NCT01761877
• Recruitment Status: Active, not recruiting
• First Posted: January 7, 2013
• Last Update Posted: November 30, 2018
• Sponsor: Stony Brook University
• Information provided by (Responsible Party): Alison Stopeck, Stony Brook University

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.

Condition or disease	Intervention/treatment	Phase
Inflammation; Cancer; Pain; Hypertension	Drug: Sulindac	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NSAID Effects on Clinical and Imaging Breast Biomarkers
• Study Start Date: December 2012
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: June 2019

Arms and Interventions

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 Name: Clinoril
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.

Outcome Measures

Primary Outcome Measures :

1. Change in breast density measured as fat to water ratio by magnetic resonance imaging [ Time Frame: Baseline and 16 months ]

Secondary Outcome Measures :

1. Muscle and joint pain and stiffness [ Time Frame: Baseline and 16 months ]

Other Outcome Measures:

1. Clinically significant change in blood pressure [ Time Frame: Baseline and 16 months ]

Eligibility Criteria

• Ages Eligible for Study: up to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

University of Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, New York

Stony Brook University Cancer Center

Stony Brook, New York, United States, 11794

Sponsors and Collaborators

Stony Brook University

Investigators

• 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

More Information

• Responsible Party: Alison Stopeck, Professor, Stony Brook University
• ClinicalTrials.gov Identifier: NCT01761877
• Other Study ID Numbers: 1RO1 CA1615301A1; 12-0080-04 ( Other Identifier: UArizona ); 676847 ( Other Identifier: Stony Brook University )
• First Posted: January 7, 2013
• Last Update Posted: November 30, 2018
• Last Verified: November 2018

• 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

Keywords provided by Alison Stopeck, Stony Brook University:

breast cancer, nonsteroidal antiinflammatory drug , breast density, chemoprevention, aromatase inhibitors

Additional relevant MeSH terms:

Inflammation; Pathologic Processes; Sulindac; 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; Antineoplastic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action