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 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|
- 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 ]
- Muscle and joint pain and stiffness [ Time Frame: Baseline and 16 months ] [ Designated as safety issue: No ]
- Clinically significant change in blood pressure [ Time Frame: Baseline and 16 months ] [ Designated as safety issue: Yes ]
|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)|
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01761877
|Contact: Patricia Caterina Vacchi-Suzzi, PhDemail@example.com|
|Contact: Patricia Delli Bovi, RN||631 638 firstname.lastname@example.org|
|United States, Arizona|
|University of Arizona Cancer Center||Recruiting|
|Tucson, Arizona, United States, 85724|
|Contact: Amy Carrier, RN 520-318-7115 email@example.com|
|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 firstname.lastname@example.org|
|Contact: Caterina Vacchi-Suzzi, PhD 6314448074 email@example.com|
|Principal Investigator: Alison Stopeck, MD|
|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|