Metformin Hydrochloride in Patients With Atypical Hyperplasia or In Situ Breast Cancer to Placebo in Decreasing Atypical Cells in Patients With Atypical Hyperplasia or in Situ Breast Cancer
This randomized phase III trial studies metformin hydrochloride to see how well it works compared to placebo in decreasing atypical cells in patients with atypical hyperplasia or in situ breast cancer.
Atypical Ductal Breast Hyperplasia
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Ductal Breast Carcinoma in Situ
Lobular Breast Carcinoma in Situ
Drug: metformin hydrochloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Testing for Atypia in Random Periareolar Fine Needle Aspiration (RPFNA) Cytology After 12 Months Metformin (1,1-Dimethylbiguanide Hydrochloride) Chemoprevention Versus Placebo Control in Premenopausal Women|
- Test for the presence or absence of atypia in RPFNA after 12 months and 24 months. Month 24 is optional for the placebo group for those patients who remain on the placebo arm and will not receive metformin (Metformin versus placebo control). [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
- Test for the Masood Score and the presence of atypia or disapperance of atypia in RPFNA after 12 months (for both arms) and 24 months for Metformin arm. [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
- Test the reproducibility of RPPM in duplicate RPPM determination from single bilateral RPFNA specimen. [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
- Determine the change in percent breast density from prior to the initiation of metformin or placebo treatment through therapy (ie, Months 12 and 24) and following therapy (Months 36 and 48). [ Time Frame: Baseline up to 48 months ] [ Designated as safety issue: No ]
- Compare Masood Cytology Score value at 0, 12 and 24 months in right and left breast from the same individual in the metformin and non-metformin group. [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
- Correlate baseline RPPM values with presence of atypia at Month 12 and Month 24. [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||August 2013|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm I: metformin hydrochloride
Patients will receive metformin hydrochloride tablet 850 mg PO BID for 24 months on Arm I, which includes a 4-week ramp up of 850 mg PO QD.
Drug: metformin hydrochloride
Placebo Comparator: Arm II: placebo
Patients receive placebo tablet PO QD BID for 12 months which includes a 4-week ramp up of 850 mg PO QD. Patients initially randomized to the placebo group (Arm II) may crossover to the metformin group (Arm I) for months 13-24.
Other Name: PLCB
Patients are randomized to 1 of 2 treatment groups. Patients will receive metformin hydrochloride 850 mg by mouth (PO) twice daily (BID) for 24 months on Arm I, which includes a 4-week ramp up of 850 mg PO QD. Patients will receive placebo 850 mg PO BID for 12 months on Arm II, which includes a 4-week ramp up of 850 mg PO QD. Patients initially randomized to the placebo (Arm II) may crossover to the metformin hydrochloride treatment group (Arm I) for months 13-24. The primary and secondary objectives are described below.
• Test for the presence or absence of cytological atypia in random periareolar fine needle aspiration (RPFNA) bilateral aspirates for women receiving metformin versus placebo control.
- Use the Masood Cytology Index Score to test for the presence of cytological atypia or disappearance of cytological atypia in RPFNA bilateral aspirates.
- Compare Masood Cytology Score values in the right and left breasts from the same individual in the metformin and placebo groups.
- Test the reproducibility of reverse phase protein microarray (RPPM) in duplicate RPPM determinations from individual RPFNA specimens.
- Correlate baseline RPPM values with presence of atypia (as measured by Masood Cytology Index Score).
- Determine the change in percent breast density.
After completion of study treatment, patients are followed up for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01905046
|Study Chair:||Victoria Seewaldt, M.D.||Duke University School of Medicine - Department of Pharmacology and Cancer Biology|