Breast Cancer, Breast Tumors
Conditions
Keywords
breast, cancer, doxorubicin, metformin, cardiotoxicity, ejection fraction, LVEF
Brief summary
The goal of this study is to determine if co-administration of metformin and doxorubicin in breast cancer patients receiving neoadjuvant or adjuvant therapy will reduce the number of patients who develop a significant change in left ventricle ejection fraction (LVEF).
Detailed description
This is a randomized, open-label, phase II design pilot study in patients with breast cancer requiring neoadjuvant or adjuvant chemotherapy. Eligible patients will be equally randomized to either receive metformin plus standard of care therapy or standard of care therapy alone. Patients receiving metformin will continue drug until the doxorubicin-containing cycles are complete, unless unacceptable toxicity occurs or the patient decides to withdraw from the study. Both arms of the study will undergo echocardiograms with contrast at baseline, upon completion of doxorubicin-containing cycles (within 28 days of completion), and at the one-year and seven-year time points. Additionally biomarker labs will be obtained to explore if there is a correlation between change in cardiac activity and the activity of metformin. If willing, all enrolled patients will provide a sample of whole blood for further exploratory analysis. Symptoms reported during the study will be correlated with know single nucleotide polymorphisms (SNPs) found during an exploratory genomic analysis.
Interventions
DRUGMetformin
Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy.
DRUGDoxorubicin
Standard of care treatment with doxorubicin
Sponsors
Avera McKennan Hospital & University Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Breast cancer requiring neoadjuvant or adjuvant therapy with doxorubicin * Complete metabolic panel demonstrating adequate organ functions as defined by the following: Aspartate transaminase (AST) less than 2.5 times Upper Limit of Normal (ULN); Alanine transaminase (ALT) less than 2.5 times ULN; alkaline phosphatase less than 2.5 times ULN; serum creatinine less than 1.5 mg/dL; serum bilirubin less than ULN * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Age greater than or equal to 21 years
Exclusion criteria
* Known diabetes * History of cardiac arrhythmias or symptomatic cardiac disease * Currently taking antiarrhythmic medications, beta-blockers, or other rate controlling cardiac medications * Currently taking metformin and/or sulfonylureas * Known hypersensitivity or intolerance to metformin * Baseline ejection fraction of less than 50% measured by echocardiogram * Known hypersensitivity to contrast used during echocardiogram * Risk factors associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heard failure, history of acidosis, habitual intake of 3 or more alcoholic beverages per day) * Pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram | 1 year | Determine whether the addition of metformin to standard doxorubicin therapy in breast cancer patients will decrease the incidence of change in left ventricle ejection fraction (LVEF). |
Countries
United States
Participant flow
Recruitment details
Referrals and investigator's own patients
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin.
Doxorubicin: Standard of care treatment with doxorubicin | 14 |
| Metformin + Standard of Care Patients will receive metformin during their treatment with doxorubicin for their breast cancer.
Metformin: Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy.
Doxorubicin: Standard of care treatment with doxorubicin | 16 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Study Termination | 1 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Standard of Care | Metformin + Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 26 Participants |
| Age, Continuous | 43 years | 53 years | 53 years |
| Echocardiography | 14 participants | 16 participants | 30 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 16 Participants | 30 Participants |
| Region of Enrollment United States | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 12 / 14 | 16 / 16 |
| serious Total, serious adverse events | 0 / 14 | 3 / 16 |
Outcome results
Primary
Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram
Determine whether the addition of metformin to standard doxorubicin therapy in breast cancer patients will decrease the incidence of change in left ventricle ejection fraction (LVEF).
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care | Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram | 4 Participants |
| Metformin + Standard of Care | Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram | 5 Participants |