Trial Outcomes & Findings for Simvastatin in Preventing a New Breast Cancer in Women at High Risk for a New Breast Cancer (NCT NCT00334542)

NCT ID: NCT00334542

Last Updated: 2019-04-03

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: Baseline and week 24
• Results posted on: 2019-04-03

Participant Flow

Participants were required to have good performance status, intact contralateral breast, and be at least 3 months from planned local and systemic adjuvant treatment.

Participant milestones

Measure	Simvastatin Simvastatin 40 mg for 24-28 weeks
Overall Study STARTED	50
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Simvastatin Simvastatin 40 mg for 24-28 weeks
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	1
Overall Study New cancer diagnosis	1

Baseline Characteristics

Simvastatin in Preventing a New Breast Cancer in Women at High Risk for a New Breast Cancer

Baseline characteristics by cohort

Measure	Simvastatin n=50 Participants Simvastatin 40 mg for 24-28 weeks
Age, Continuous	53 years n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	47 Participants n=5 Participants
Race/Ethnicity, Customized African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Region of Enrollment United States	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: Paired baseline and post-simvastatin treatment fasting lipid samples were available for 47 participants, including 45 women who completed the study and from two who discontinued the drug prior to the completion of the 24-28 weeks of drug, and are integrated in the intention-to-treat analyses

Outcome measures

Measure	Simvastatin n=47 Participants Simvastatin 40 mg for 24-28 weeks
Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline hsCRP	-0.15 mg/dl Interval -1.0 to 0.0
Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline Total cholesterol	-54 mg/dl Interval -58.5 to -39.0
Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline High-density lipoprotein cholesterol (HDL)	-1 mg/dl Interval -2.0 to 3.0
Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline Estrogen (estrone sulfate)	-81.5 mg/dl Interval -225.5 to -40.5

PRIMARY outcome

Timeframe: Baseline and week 24

Population: Paired baseline and post-simvastatin treatment mammograms for evaluation of breast density were available for 43 participants.

Outcome measures

Measure	Simvastatin n=43 Participants Simvastatin 40 mg for 24-28 weeks
Change in a Panel of Biomarkers (Contralateral Breast Density) From Baseline	-0.78 percentage of change Interval -2.0 to 1.2

SECONDARY outcome

Timeframe: Change from Baseline to week 24

Population: Methylation values at both time points were only evaluable in 17 participants.

Median change in gene promotor methylation (%M) in the contralateral breast of women with breast cancer after six months of therapy

Outcome measures

Measure	Simvastatin n=17 Participants Simvastatin 40 mg for 24-28 weeks
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation CyclinD2 (CCND2)	0.5 percent methylation (%M) Interval -0.68 to 1.97
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation SCGB3A1	0 percent methylation (%M) Interval -1.9 to 2.43
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation TWIST1	0.21 percent methylation (%M) Interval -1.08 to 0.85
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation RASSF1	0 percent methylation (%M) Interval -1.11 to 1.63
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation RARB	-0.08 percent methylation (%M) Interval -1.72 to 0.23
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation APC	0.01 percent methylation (%M) Interval -0.14 to 0.75
Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation CMI	-0.42 percent methylation (%M) Interval -2.14 to 2.92

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Enough tissue was not collected to assess this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Simvastatin n=50 participants at risk Simvastatin 40 mg for 24-28 weeks
Gastrointestinal disorders Constipation	14.0% 7/50 • Number of events 7 • up to 28 weeks Adverse events data were collected during 24-28 weeks of simvastatin administration
Nervous system disorders Headache	8.0% 4/50 • Number of events 4 • up to 28 weeks Adverse events data were collected during 24-28 weeks of simvastatin administration
Skin and subcutaneous tissue disorders Rash maculo-papular	2.0% 1/50 • Number of events 1 • up to 28 weeks Adverse events data were collected during 24-28 weeks of simvastatin administration
Musculoskeletal and connective tissue disorders Muscle weakness	10.0% 5/50 • Number of events 5 • up to 28 weeks Adverse events data were collected during 24-28 weeks of simvastatin administration
Musculoskeletal and connective tissue disorders Myalgia	10.0% 5/50 • Number of events 5 • up to 28 weeks Adverse events data were collected during 24-28 weeks of simvastatin administration

Additional Information

Dr. Vered Stearns

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 4432876489

Email: vstearn1@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place