Trial Outcomes & Findings for NSAID Effects on Clinical and Imaging Breast Biomarkers (NCT NCT01761877)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Baseline and 12 months

Results posted on

2023-02-10

Participant Flow

All patients were enrolled at the University of Arizona Cancer Center and at the Stony Brook Cancer Center.

Patients assigned to receive sulindac were required to complete a NSAID washout period.

Participant milestones

Participant milestones
Measure	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. Sulindac	Observational Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their standard of care treatment and be monitored with MRI for change in breast density every 6 and 12 months.
Overall Study STARTED	58	56
Overall Study COMPLETED	43	40
Overall Study NOT COMPLETED	15	16

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Sulindac	Observational Women taking aromatase inhibitors for adjuvant therapy for their breast cancer will continue their standard of care treatment and be monitored with MRI for change in breast density every 6 and 12 months.
Overall Study Adverse Event	7	0
Overall Study Withdrawal by Subject	6	4
Overall Study Stopped taking AI Aromatase Inhibitor	1	5
Overall Study Death	0	1
Overall Study MRI intolerant	1	6

Baseline Characteristics

NSAID Effects on Clinical and Imaging Breast Biomarkers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulindac (Clinoril) n=50 Participants 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. Sulindac	Observational n=50 Participants 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 at 6 and 12 months.	Total n=100 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 5.5 • n=99 Participants	64.2 years STANDARD_DEVIATION 6.6 • n=107 Participants	63.4 years STANDARD_DEVIATION 6.1 • n=206 Participants
Sex: Female, Male Female	50 Participants n=99 Participants	50 Participants n=107 Participants	100 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized White, Non-Hispanic	44 Participants n=99 Participants	46 Participants n=107 Participants	90 Participants n=206 Participants
Race/Ethnicity, Customized Black, Non-Hispanic	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized Asian, Non-Hispanic	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Region of Enrollment United States	50 Participants n=99 Participants	50 Participants n=107 Participants	100 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and 12 months

Population: Breast density data were unavailable for 4 participants in the observation group due to MRI intolerance. This reduced the sample size for the outcome of change in breast density for the observation arm compared to the secondary endpoints.

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

Outcome measures

Outcome measures
Measure	Sulindac (Clinoril) n=50 Participants 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. Sulindac	Observational n=46 Participants 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 every 6 months for up to 12 months.
Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging	-9.8 percent change in breast density Interval -14.6 to -4.7	-3.6 percent change in breast density Interval -8.9 to 2.0

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: Questionnaires for patient reported outcomes were completed at baseline for 50 participants in both sulindac and the observation group.

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.

Outcome measures

Outcome measures
Measure	Sulindac (Clinoril) n=50 Participants 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. Sulindac	Observational n=50 Participants 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 every 6 months for up to 12 months.
Muscle and Joint Pain and Stiffness	-5.85 score on a scale Interval -9.73 to -1.96	-0.25 score on a scale Interval -3.25 to 2.69

OTHER_PRE_SPECIFIED outcome

Timeframe: Change in blood pressure between Baseline and 12 months

Population: Blood pressure was available at baseline for 50 participants in both the sulindac and observation group.

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

Outcome measures

Outcome measures
Measure	Sulindac (Clinoril) n=50 Participants 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. Sulindac	Observational n=50 Participants 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 every 6 months for up to 12 months.
Change in Mean Arterial Blood Pressure at 12 Months	0.77 mm Hg Interval -1.82 to 3.0	1.52 mm Hg Interval -1.17 to 4.0

Adverse Events

Sulindac (Clinoril)

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Observational

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Sulindac (Clinoril) n=50 participants at risk 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 and two breast biopsies.	Observational n=50 participants at risk 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 every 6 months for up to 12 months.
Nervous system disorders Intraparenchymal Hemorrhage associated with cerebral amyloid angiopathy	2.0% 1/50 • Number of events 1 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	0.00% 0/50 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Gastrointestinal disorders Transient Pancreatitis of Unclear Etiology	2.0% 1/50 • Number of events 1 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	0.00% 0/50 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Blood and lymphatic system disorders B cell Lymphoma	2.0% 1/50 • Number of events 1 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	0.00% 0/50 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Gastrointestinal disorders Antral Gastritis	2.0% 1/50 • Number of events 1 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	0.00% 0/50 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) death	0.00% 0/50 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	2.0% 1/50 • Number of events 1 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.

Other adverse events

Other adverse events
Measure	Sulindac (Clinoril) n=50 participants at risk 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 and two breast biopsies.	Observational n=50 participants at risk 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 every 6 months for up to 12 months.
Gastrointestinal disorders upset stomach or pain	12.0% 6/50 • Number of events 6 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Skin and subcutaneous tissue disorders rash	6.0% 3/50 • Number of events 3 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Nervous system disorders headache	6.0% 3/50 • Number of events 3 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Metabolism and nutrition disorders hyperglycemia	6.0% 3/50 • Number of events 3 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Vascular disorders hypertension	14.0% 7/50 • Number of events 7 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.
Psychiatric disorders insomnia	6.0% 3/50 • Number of events 3 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.	— 0/0 • Adverse event data were collected over 13 months. Participants in the observation only group were not systematically followed for adverse events. There was not active intervention and there was not intent to compare the two groups.

Additional Information

Dr. Alison T Stopeck

Stony Brook University

Phone: 5206476982

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place