NSAID Effects on Clinical and Imaging Breast Biomarkers

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Stony Brook University
Sponsor:
Information provided by (Responsible Party):
Alison Stopeck, Stony Brook University
ClinicalTrials.gov Identifier:
NCT01761877
First received: December 28, 2012
Last updated: July 14, 2015
Last verified: July 2015
  Purpose

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 Intervention Phase
Inflammation
Cancer
Pain
Hypertension
Drug: Sulindac
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: NSAID Effects on Clinical and Imaging Breast Biomarkers

Resource links provided by NLM:


Further study details as provided by Stony Brook University:

Primary Outcome Measures:
  • Change in breast density measured as fat to water ratio by magnetic resonance imaging [ Time Frame: Baseline and 16 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Muscle and joint pain and stiffness [ Time Frame: Baseline and 16 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Clinically significant change in blood pressure [ Time Frame: Baseline and 16 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 175
Study Start Date: December 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761877

Contacts
Contact: Patricia Caterina Vacchi-Suzzi, PhD 6314448074 caterina.vacchi-suzzi@stonybrookmedicine.edu
Contact: Patricia Delli Bovi, RN 631 638 0852 patricia.dellibovi@stonybrookmedicine.edu

Locations
United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Amy Carrier, RN    520-318-7115    amyrc@email.arizona.edu   
Principal Investigator: Pavani Chalasani, MD         
United States, New York
Stony Brook University Cancer Center Recruiting
Stony Brook, New York, United States, 11794
Contact: Patricia Delli Bovi, RN    631-638-0852    patricia.dellibovi@stonybrookmedicine.edu   
Contact: Caterina Vacchi-Suzzi, PhD    6314448074    caterina.vacchi-suzzi@stonybrookmedicine.edu   
Principal Investigator: Alison Stopeck, MD         
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

No publications provided

Responsible Party: Alison Stopeck, Professor, Stony Brook University
ClinicalTrials.gov Identifier: NCT01761877     History of Changes
Other Study ID Numbers: 1RO1 CA1615301A1, 12-0080-04, 676847
Study First Received: December 28, 2012
Last Updated: July 14, 2015
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by Stony Brook University:
breast cancer, nonsteroidal antiinflammatory drug , breast density, chemoprevention, aromatase inhibitors

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Aromatase Inhibitors
Sulindac
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015