Trial Outcomes & Findings for Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer (NCT NCT01905046)
NCT ID: NCT01905046
Last Updated: 2025-04-13
Results Overview
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE3
Target enrollment
86 participants
Primary outcome timeframe
12 months
Results posted on
2025-04-13
Participant Flow
Participant milestones
| Measure |
Arm I
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12. Then patients receive Metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
|---|---|---|
|
Months 0-12
STARTED
|
42
|
44
|
|
Months 0-12
COMPLETED
|
42
|
44
|
|
Months 0-12
NOT COMPLETED
|
0
|
0
|
|
Months 13-24
STARTED
|
42
|
44
|
|
Months 13-24
COMPLETED
|
25
|
29
|
|
Months 13-24
NOT COMPLETED
|
17
|
15
|
Reasons for withdrawal
| Measure |
Arm I
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12. Then patients receive Metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
|---|---|---|
|
Months 13-24
Withdrawal by Subject
|
10
|
10
|
|
Months 13-24
Adverse Event
|
3
|
2
|
|
Months 13-24
Protocol Violation
|
3
|
3
|
|
Months 13-24
Physician Decision
|
1
|
0
|
Baseline Characteristics
Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer
Baseline characteristics by cohort
| Measure |
Arm I
n=42 Participants
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II
n=44 Participants
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12. Then Metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.7 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
41.9 years
STANDARD_DEVIATION 7.3 • n=7 Participants
|
41.3 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Per protocol, evaluable patients are defined as having a baseline Masood score between 14 and 17 in at least one breast, and all evaluable breasts undergo satisfactory RPFNA at 12 months. At the time of the primary analysis, we had 66 evaluable patients out of 86 randomized patients (32 Placebo, 34 Metformin).
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.
Outcome measures
| Measure |
Arm I
n=32 Participants
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II
n=34 Participants
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12. Then Metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
|---|---|---|
|
Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
With Aytpia
|
20 Participants
|
21 Participants
|
|
Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
Without Aytpia
|
12 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Up to 24 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 24 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 24 monthsOutcome measures
Outcome data not reported
Adverse Events
Arm I
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
Arm II Months 0-12: Placebo
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
Arm II Months 13-24: Metformin
Serious events: 2 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm I
n=42 participants at risk
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II Months 0-12: Placebo
n=44 participants at risk
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12.
|
Arm II Months 13-24: Metformin
n=57 participants at risk
Patients recieve metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Vascular disorders
Thromboembolic event
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
Other adverse events
| Measure |
Arm I
n=42 participants at risk
Patients receive metformin hydrochloride 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12
|
Arm II Months 0-12: Placebo
n=44 participants at risk
Patients receive placebo 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 2-12.
|
Arm II Months 13-24: Metformin
n=57 participants at risk
Patients recieve metformin 850 mg p.o. daily for 4 weeks, then 850 mg p.o. b.i.d. for months 14-24.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Eye disorders
Eye pain
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Eye disorders
Photophobia
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Gastrointestinal disorders
Abdominal distension
|
4.8%
2/42 • Number of events 2 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
5.3%
3/57 • Number of events 3 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/42 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
1.8%
1/57 • Number of events 3 • 24 months
|
|
Gastrointestinal disorders
Bloating
|
14.3%
6/42 • Number of events 7 • 24 months
|
27.3%
12/44 • Number of events 17 • 24 months
|
17.5%
10/57 • Number of events 11 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/42 • 24 months
|
6.8%
3/44 • Number of events 3 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Diarrhea
|
28.6%
12/42 • Number of events 19 • 24 months
|
59.1%
26/44 • Number of events 35 • 24 months
|
42.1%
24/57 • Number of events 34 • 24 months
|
|
Gastrointestinal disorders
Dry mouth
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/42 • 24 months
|
4.5%
2/44 • Number of events 3 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Gastrointestinal disorders
Flatulence
|
7.1%
3/42 • Number of events 4 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
7.0%
4/57 • Number of events 4 • 24 months
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Gastrointestinal disorders
Nausea
|
19.0%
8/42 • Number of events 10 • 24 months
|
31.8%
14/44 • Number of events 21 • 24 months
|
24.6%
14/57 • Number of events 19 • 24 months
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Vomiting
|
4.8%
2/42 • Number of events 2 • 24 months
|
18.2%
8/44 • Number of events 9 • 24 months
|
3.5%
2/57 • Number of events 2 • 24 months
|
|
General disorders
Fatigue
|
4.8%
2/42 • Number of events 2 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
General disorders
Flu like symptoms
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
General disorders
Pain
|
4.8%
2/42 • Number of events 2 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
5.3%
3/57 • Number of events 3 • 24 months
|
|
Infections and infestations
Bronchial infection
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 2 • 24 months
|
0.00%
0/57 • 24 months
|
|
Infections and infestations
Infections and infestations - Oth spec
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Infections and infestations
Skin infection
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Injury, poisoning and procedural complications
Bruising
|
4.8%
2/42 • Number of events 2 • 24 months
|
9.1%
4/44 • Number of events 4 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Investigations
Weight loss
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/42 • 24 months
|
4.5%
2/44 • Number of events 4 • 24 months
|
0.00%
0/57 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.4%
1/42 • Number of events 1 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Nervous system disorders
Dizziness
|
2.4%
1/42 • Number of events 1 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
0.00%
0/57 • 24 months
|
|
Nervous system disorders
Headache
|
4.8%
2/42 • Number of events 3 • 24 months
|
4.5%
2/44 • Number of events 3 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Nervous system disorders
Muscle weakness left-sided
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Nervous system disorders
Paresthesia
|
2.4%
1/42 • Number of events 1 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Psychiatric disorders
Agitation
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 2 • 24 months
|
0.00%
0/57 • 24 months
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 2 • 24 months
|
|
Psychiatric disorders
Depression
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Psychiatric disorders
Insomnia
|
2.4%
1/42 • Number of events 1 • 24 months
|
4.5%
2/44 • Number of events 2 • 24 months
|
0.00%
0/57 • 24 months
|
|
Reproductive system and breast disorders
Breast pain
|
2.4%
1/42 • Number of events 1 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Reproductive system and breast disorders
Pelvic pain
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
0.00%
0/42 • 24 months
|
2.3%
1/44 • Number of events 1 • 24 months
|
0.00%
0/57 • 24 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/42 • 24 months
|
0.00%
0/44 • 24 months
|
1.8%
1/57 • Number of events 1 • 24 months
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
|
Vascular disorders
Hypertension
|
2.4%
1/42 • Number of events 1 • 24 months
|
0.00%
0/44 • 24 months
|
0.00%
0/57 • 24 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place