Breast CancerPhase 2NCT02472353
Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer
A Phase 2 study testing Metformin and Doxorubicin in people with Breast Cancer and Breast Tumors, run by Avera McKennan Hospital & University Health Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Breast Cancer, Breast Tumors
- What is being tested?
- Metformin and Doxorubicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to 23 May 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
About this study
Official title: A Phase II Pilot Study Using Metformin to Reduce Cardiac Toxicity in Breast Cancer Patients
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).
Read the 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.
- Conditions
- Breast Cancer, Breast Tumors
- Being tested
- Metformin, Doxorubicin
- Keywords
- breast, cancer, doxorubicin, metformin, cardiotoxicity, ejection fraction, LVEF
- Medical subject headings
- Breast Neoplasms, Neoplasms, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
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.
DoxorubicinDrug
Standard of care treatment with doxorubicin
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. Receives: Drug: Doxorubicin |
| Metformin + Standard of Care | Experimental | Patients will receive metformin during their treatment with doxorubicin for their breast cancer. Receives: Drug: Metformin; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJul 2014
- Primary completion23 May 2018
- Study completion23 May 2018
Why it stopped: did not meet target accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avera McKennan Hospital & University Health Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kirstin Williams, CNP, Principal investigator, Avera McKennan Hospital & University Health Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472353
- Sponsor's protocol ID
- AMEM-2014-MET001
- Status last verified
- Sep 2019
- First submitted
- 9 Jun 2015
- Last updated
- 16 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sun ML, Dong JM, Liu C, Li P, Zhang C, Zhen J, Chen W. Metformin-mediated protection against doxorubicin-induced cardiotoxicity. Biomed Pharmacother. 2024 Nov;180:117535. doi: 10.1016/j.biopha.2024.117535. Epub 2024 Oct 15.
PubMed 39405911
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Pilot Study Using Metformin to Reduce Cardiac Toxicity in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02472353
- Acronym / sponsor ID
- AMEM-2014-MET001
- Conditions
- Breast Cancer, Breast Tumors
- Keywords
- breast, cancer, doxorubicin, metformin, cardiotoxicity, ejection fraction, LVEF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: did not meet target accrual
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Avera McKennan Hospital & University Health CenterUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- 23 May 2018 (actual)
- Study completion
- 23 May 2018 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Posted 16 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Drug: DoxorubicinPatients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. |
| Metformin + Standard of Care | Experimental | Drug: Metformin, Drug: DoxorubicinPatients will receive metformin during their treatment with doxorubicin for their breast cancer. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageMetformin 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. | Drug | Metformin + Standard of Care |
| DoxorubicinStandard of care treatment with doxorubicin | Drug | Metformin + Standard of Care, Standard of Care |
Primary outcome
Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39405911Sun ML, Dong JM, Liu C, Li P, Zhang C, Zhen J, Chen W. Metformin-mediated protection against doxorubicin-induced cardiotoxicity. Biomed Pharmacother. 2024 Nov;180:117535. doi: 10.1016/j.biopha.2024.117535. Epub 2024 Oct 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kirstin Williams, CNP principal investigator
Avera McKennan Hospital & University Health Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin and Doxorubicin in people with Breast Cancer and Breast Tumors, run by Avera McKennan Hospital & University Health Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02472353, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2019.