Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cicatrix

Inflammation

Adenocarcinoma

Cardiotoxicity

Edema

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Paaladinesh Thavendiranathan, MD

Bernd Wintersperger, MD

Breast cancer is the most common cancer amongst Canadian women. 15-20% of early breast cancers have high levels of a protein called HER2 which is associated with worse survival. Treatment of these patients with anthracyclines followed by trastuzumab (which targets HER2) improves survival. Unfortunately, these medications together can cause heart muscle injury resulting in heart dysfunction or failure in about 14% and 3.6% of the patients, respectively. Once heart failure (HF) occurs, about 60% of patients will not live past 2 years. Studies have suggested that patients with heart injury caused by anthracyclines may be more likely to develop HF with addition of trastuzumab. Therefore tests to find early heart injury after anthracyclines may allow doctors to start heart protective medications with the hope of preventing HF. Also, animal and small patient studies have shown that an increase in the water levels of the heart muscle (edema) may be an early sign of heart injury from anthracyclines. Cardiac MRI is a unique technique that has been shown to detect edema in various heart diseases.

The investigators will test the theory that, in women receiving treatment for breast cancer, heart edema detected by MRI at the end of anthracyclines will identify patients who will later develop heart dysfunction. MRI studies with novel techniques will be done pre-therapy, after anthracyclines, during herceptin, and at end of all therapy. The investigators will compare patients with and without heart dysfunction to test if patients with heart dysfunction are more likely to have edema after anthracyclines. Ultimately the investigators hope to use cardiac MRI to identify high risk patients and study various heart protective medications to prevent HF. This will improve the personal health of cancer patients by allowing them to live free of heart disease after their cancer therapy. Ultimately at a population level this will allow doctors to provide care that can be uniquely designed for each patient based on their individual risk.

The first 136 patients enrolled are included in the first part of the study, named EMBRACE-MRI 1. Enrollment for this part of the study is complete.

The remaining 44 patients will be enrolled into EMBRACE-MRI 2, which includes slight differences in obtaining sequences in MRI imaging.

Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI

Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI - The EMBRACE MRI Study

Myocardial edema is defined as an 8% increase in segmental T2 values measured in milliseconds in at least 2 myocardial segments at either of the 2 early time points. Cardiotoxicity is defined as Cardiac Magnetic Resonance Imaging (CMR) measured (1) ≥5% absolute reduction in Left Ventricular Ejection Fraction (LVEF) from baseline to an LVEF \<55% with signs or symptoms of HF, OR (2) a ≥10% absolute reduction in LVEF from baseline to \<55% without accompanying signs or symptoms at the time points when CMR is obtained OR (3) the same amount of reduction in LVEF as above, identified by echo at any time point (done every 3 months) and confirmed by CMR at that time.

Canadian Institutes of Health Research (CIHR)

University of Toronto

University Health Network, Toronto

Heart Failure

Hypoglycemic Agents

All Drugs and Chemicals

Dapagliflozin

Sodium-Glucose Transporter 2 Inhibitors

Dapagliflozin 10 mg tablet orally once daily for 12 months

Placebo tablet matching dapagliflozin orally once daily for 12 months

Placebo

Bartosz Krakowiak, PhD, MD

Rafał Matkowski, PhD, MD

Paweł Krzesiński, PhD, MD

Waldemar Banasiak, PhD, MD

The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of cancer therapeutics-related cardiac dysfunction in patients with breast cancer receiving anthracycline treatment.

This is a multicentre, randomised, double-blind, placebo-controlled phase III study, evaluating the effect of dapagliflozin versus placebo on prevention of cardiotoxicity in breast cancer patients undergoing anthracycline-based chemotherapy.

CardioPROTECTion With Dapagliflozin in Breast Cancer Patients Treated With AnthrAcycline - PROTECTAA TRIAL

A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Study, Evaluating the Effect of Dapagliflozin on Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy

Incidence of cancer therapeutics related cardiac dysfunction defined as:

1. the appearance of heart failure symptoms (NYHA class I-IV) due to an impairment of heart function or structure within 12 months; or
2. asymptomatic decrease in left ventricular ejection fraction \> 10% after 12 months; or
3. asymptomatic decrease in left ventricular ejection fraction \< 10% but up to 40-49% after 12 months; or
4. asymptomatic decrease in global left ventricular longitudinal strain \>15% after 12 months; or
5. asymptomatic increase in biomarkers (troponin I \> upper reference limit (99th centile) and increase of at least 30% from pre-treatment concentration or NTproBNP \> 125 pg/ml and increase of at least 30% from baseline) after 12 months.

Incidence of cancer therapeutics related cardiac dysfunction defined as:

1. emergence of heart failure symptoms (NYHA class I-IV) due to impaired cardiac function or structure at 6 months; or
2. decrease LVEF \> 10% after 6 months; or
3. decrease LVEF \< 10% but to a value of 40-49% after 6 months; or
4. a decrease in global longitudinal strain of \> 15% after 6 months; or
5. asymptomatic increase in biomarkers (troponin I \> upper reference limit (99th centile) and an increase of at least 30% from pre-treatment concentration or NTproBNP \>125pg/ml and an increase of at least 30% from baseline) after 6 months.

Assessed by transthoracic echocardiography.

Assessed as the ratio of E/E', i.e. maximum mitral annular inflow velocity during the rapid ventricular filling phase, to maximum mitral annular motion velocity by tissue Doppler during the rapid ventricular filling phase.

The EQ-5D questionnaire consists of two parts: descriptive one, which measures five dimensions of health (mobility, self care, usual activities, pain \& discomfort, anxiety \& depression) and EQ Visual Analogue Scale numbered from 0 to 100, where higher value indicate better self-reported health.

Secondary safety endpoint. Occurrence of death from cardiovascular causes, nonfatal myocardial infarction, non-fatal stroke.

Secondary safety endpoint. Hypoglycaemia is defined as serum glucose level 3 mmol/l (\<54 mg/dl) with coexisting related clinical symptoms.

Secondary safety endpoint, defined as occurrence of:

* Sodium plasma level of \>150 mmol/L
* Potassium plasma level of \>6.0 mmol/L

Secondary safety endpoint. Defined as:

* sustained (i.e. \>28 days) decline in eGFR ≥50% AND/OR
* reaching end stage renal disease defined as:

  * sustained (i.e. \>28 days) eGFR \<15 mL/min/1.73 m2
  * chronic dialysis treatment
  * receiving a renal transplant AND/OR
* renal death

Secondary safety endpoint. Any unexpected adverse drug reaction (UADR).

Secondary safety endpoint. Any hypersensitivity reaction with proven immunological pathomechanism (types I-IV according to Coombs and Gell).

Secondary safety endpoint. Any symptomatic infection (viral, bacterial or fungal).

4th Military Clinical Hospital with Polyclinic, Poland

Antineoplastic Agents

Anti-Infective Agents

Metformin

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin.

Patients will receive metformin during their treatment with doxorubicin for their breast cancer.

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.

Standard of care treatment with doxorubicin

Kirstin Williams, CNP

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).

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.

Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

A Phase II Pilot Study Using Metformin to Reduce Cardiac Toxicity in Breast Cancer Patients

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).

Avera McKennan Hospital & University Health Center

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

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

Metformin + Standard of Care

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Echocardiography

The study was terminated early due to slow accrual.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI	NCT02306538	Breast Neoplasm...		18 Years -	University Health Network, Toronto
Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI	NCT02306538	Breast Neoplasm...		18 Years -	University Health Network, Toronto
Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI	NCT02306538	Breast Neoplasm...		18 Years -	University Health Network, Toronto
CardioPROTECTion With Dapagliflozin in Breast Cancer Patients Treated With AnthrAcycline - PROTECTAA TRIAL	NCT06304857	Breast Cancer Heart Failure	Dapagliflozin Placebo	18 Years - 80 Years	4th Military Clinical Hospital with Polyclinic, Poland
Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer	NCT02472353	Breast Cancer Breast Tumors	Metformin Doxorubicin	21 Years -	Avera McKennan Hospital & University Health Center

Spots Global Cancer Trial Database for ejection fraction