Breast Carcinoma, Hematopoietic and Lymphoid Cell Neoplasm, Lymphoma, Sarcoma
Conditions
Brief summary
This phase II trial compares two drug therapy plans for the correction of heart function changes (reduced ejection function) in patients who have undergone anthracycline-based treatment for lymphoma, sarcoma, or breast cancer. Reduced ejection fraction means the left ventricle of the heart is pumping a reduced blood volume with each heartbeat. Treatment is recommended, and the purpose of this research is to compare two different drug therapy plans (standard therapy with carvedilol and lisinopril and standard therapy with carvedilol and lisinopril plus pravastatin and spironolactone) and their effects on improvement of heart function. All of these drugs are heart medications, and carvedilol and lisinopril are commonly used to improve heart function. Adding pravastatin, a cholesterol lowering drug with additional beneficial effects on the cardiovascular system, and spironolactone, a water pill with additional beneficial effects on the cardiovascular system, may lead to even better (and faster) improvements in heart function.
Detailed description
PRIMARY OBJECTIVE: I. To compare cardiac function changes (delta left ventricular ejection fraction \[LVEF\]) over six months in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone. SECONDARY OBJECTIVE: I. To compare cardiac function recovery rates over six months in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma, sarcoma, or breast cancer randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone. II. To compare the time to recovery of cardiac function in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma, sarcoma, or breast cancer randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone. OUTLINE: Patients are randomized in to 1 of 2 groups. GROUP I: Patients receive carvedilol orally (PO) and lisinopril orally (PO), up-titrated to maximum tolerated doses as per standard clinical practice for 6 months. GROUP II: Patients receive standard clinical practice therapy as in Group I. Patients also receive pravastatin PO and spironolactone PO for 6 months. After completion of study treatment, patients are followed up at the 6 month visit.
Interventions
DRUGCarvedilol
Given PO
DRUGLisinopril
Given PO
DRUGPravastatin
Given PO
DRUGSpironolactone
Given PO
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>= 18 years of age. * New diagnosis of reduced cardiac function. * Any prior anthracycline-based cancer therapy for hematological malignancy, breast cancer, or sarcoma.
Exclusion criteria
* History of heart failure (HF) of any class and type, or diagnosis of cardiomyopathy prior to anthracycline therapy. * On active therapy with a fibrate, niacin or eplerenone, or statin. * History of myopathy/rhabdomyolysis. * History of statin intolerance. * Active treatment for hyperlipidemia. * History of gout. * Active treatment for liver disease. * Unexplained persistent elevations of serum transaminases (above upper limit of normal over two weeks). * Pregnancy. * Breast-feeding. * Hyperkalemia (above upper limit of normal). * Addison disease. * Estimated glomerular filtration rate (eGFR) \< 30 mL/minute/1.73 m\^2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delta change in left ventricular ejection fraction [LVEF]) | Baseline up to 6 months | Will be a comparison of the average delta change in LVEF from start to six months of therapy between group 1 and 2 via an independent groups t-test or Wilcoxon as appropriate after testing distributional assumptions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac function recovery rates between group 1 and group 2 | Baseline up to 6 months | Incidence rates will be compared using a simple test for equality of binomial proportions (χ \^ 2 -test or Fisher Exact). |
| Time to recovery of cardiac function between group 1 and group 2 | Baseline up to 6 months | Will be a comparison of the average delta change in LVEF from start to six months of therapy between group 1 and 2 via an independent groups t-test or Wilcoxon as appropriate after testing distributional assumptions. |
Outcome results
None listed