Effect of DAPAglifozin on MYOcardial Remodeling of Breast CANCER Patients Treated with Anthracycline Based Chemotherapy (DAPA-MYOCANCER)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Anthracycline-based chemotherapy is the standard treatment for several common cancer types, including breast cancer, lymphoma and sarcoma. However, within 12 months, up to 20% of the 1,000,000 patients worldwide treated with anthracyclines each year have a significant reduction in left ventricular ejection fraction (LVEF), leading to a three to six-fold higher rates of incident heart failure. Once established, anthracycline-induced heart failure carries a poor prognosis with a 2-year survival of only 40%.
Consistent data have established that sodium-glucose transport protein 2 (SGLT2) inhibitors reduce incident heart failure in patients without cancer. There is biological plausibility and animal data to support the hypothesis central to this proposal that SGLT2 will reduce anthracycline-induced cardiotoxicity (AIC). Anthracyclines increase inflammatory cytokines, increase cell death, increase myocardial fibrosis leading to a decrease in the LVEF. In animal and cellular models, SGLT2 inhibitors reduce inflammatory cytokines, increase cell viability, reduce myocardial fibrosis and prevent the decline in LVEF with anthracyclines. There are no preliminary clinical data testing whether SGLT2 inhibitors are cardioprotective during treatment with anthracyclines among patients with breast cancer.
We propose a single-center randomized double-blind placebo-controlled trial, in 80 patients, who will be randomized 1:1 to dapagliflozin 10mg/daily or placebo to determine whether dapagliflozin started prior to anthracyclines reduces AIC in patients breast cancer. The endpoint AIC will be defined as a 6% difference in the change in LVEF between groups within the first 9 months after the start of therapy. LVEF will be measured using the gold-standard, cardiac magnetic resonance (CMR), performed in an established core clinical trials laboratory by expert researchers.
Participants will be recruited over 2 years from a large volume academic oncology network. Myocardial fibrosis is a key intermediary that occurs prior to the development of LV dysfunction. CMR is the gold-standard imaging technique for fibrosis; therefore, to test whether the sub-acute development of myocardial fibrosis can predict the late occurrence of AIC and whether dapagliflozin reduces myocardial fibrosis, we also propose measuring the extent of fibrosis at baseline and 9 months.
We hypothesize that dapagliflozin will attenuate the anthracycline-induced increase in myocardial fibrosis. Secondary and exploratory outcomes will include significant changes in myocardial perfusion assessed by stress CMR, flow-mediated vasodilatation assessed by ultrasound, exercise capacity assessed by cardiopulmonary exercise test, and biomarkers.
If successful, this study will show that dapagliflozin started prior to anthracyclines will preserve the LVEF and will attenuate the anthracycline-induced cardiovascular toxicity.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Otavio Rizzi Coelho-Filho, MD, MPH, PhD
- Phone Number: +55 19 3521-7755
- Email: tavicocoelho@gmail.com
Study Contact Backup
- Name: Joaquim Barreto Oliveira, MD
- Phone Number: +55 19 3521 7959
- Email: jba.clinicamedica@gmail.com
Study Locations
-
-
SP
-
Campinas, SP, Brazil, 13083-888
- Recruiting
- Hospital de Clinicas da UNICAMP
-
Contact:
- Joaquim B Oliveira, MD
- Phone Number: +55 19 3521 7959
- Email: jba.clinicamedica@gmail.com
-
Contact:
- Joaquim Barreto Oliveira, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Female
- Over 18 years old
- Breast cancer
- Chemotherapy as treatment planning and programmed cumulative dose equivalent to 240 mg/m2 of doxorubicin.
Exclusion Criteria:
- Contraindications for performing CMR exams, such as patients with pacemakers or cardiac defibrillators of any type, metal clips for cerebral aneurysms, cochlear implants, and ventriculoperitoneal bypass valves.
- Inability to perform CMR due to claustrophobia.
- Renal failure with a glomerular filtration rate < 30 ml/min/1.73 m2.
- Previous history of myocardial infarction, congestive heart failure, or myocardial revascularization, whether percutaneous or surgical.
- Previous history of significant valvular heart disease.
- Previous history of cardiomyopathies.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Dapagliflozin
Standard chemotherapy treatment + Dapagliflozin 10mg/day.
|
Patients in this group will receive 1 tablet of 10mg dapagliflozin daily for 9 months, starting 7-10 days before chemotherapy treatment.
|
|
Placebo Comparator: Placebo Group
Standard chemotherapy treatment + Placebo.
|
Patients in this group will receive 1 placebo tablet per day, with identical characteristics to the group receiving dapagliflozin, for 9 months, starting 7-10 days before the start of chemotherapy treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in left ventricle ejection fraction
Time Frame: 36 weeks
|
The primary outcome will be the 6% difference in the mean of left ventricle ejection fraction change, as assessed by CMR, between the placebo group and the dapagliflozin group
|
36 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Otavio Rizzi Coelho-Filho, MD, MPH, PhD, University of Campinas, Brazil
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 57488122.1.0000.5404
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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