Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors
Condition: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm
MeSH terms: Neoplasms; Heart Failure
Intervention: Carvedilol; Laboratory Biomarker Analysis; Pharmacogenomic Study; Pharmacological Study; Placebo Administration; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given PO; Correlative studies; Correlative studies; Correlative studies; Given PO; Ancillary studies; Ancillary studies
Intervention MeSH terms: Carvedilol
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 196.0
Sex: All
Healthy volunteers: No

Summary:

      This phase IIb trial studies how well low-dose carvedilol works in preventing heart failure
      in cancer survivors exposed to high dose anthracyclines for management of childhood cancer.
      Patients who received high-dose anthracycline chemotherapy are at a much greater risk for
      developing heart failure compared to survivors who didn't get any anthracycline chemotherapy.
      Heart failure happens when the heart muscle has been weakened and can't pump blood as well as
      it should. Carvedilol may help lower the risk of cardiovascular complications.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females must weigh >= 40 Kg

          -  Patient must have had a cancer diagnosis < 22 years of age, irrespective of current
             age

          -  Patient must have a lifetime cumulative anthracycline dose of >= 250 mg/m^2
             DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the
             anthracycline dose threshold must be met as part of the treatment of a cancer that was
             diagnosed at < 22 years of age

               -  Note: Institutional records (e.g., clinic note, treatment summary, chemotherapy
                  roadmap) can be used to document lifetime receipt of anthracycline dose

          -  Patient must have completed cancer treatment >= 2 years prior to study enrollment

        Exclusion Criteria:

          -  Receiving treatment for cardiomyopathy or heart failure

          -  Ejection fraction of < 50% (by radionuclide angiogram or echocardiogram) or shortening
             fraction of < 25% (by echocardiogram)

               -  Note: for instances where both are reported, and one is below the threshold, the
                  site will have the option to re-measure it centrally at the core lab

          -  Uncorrected primary obstructive or severe regurgitative valvular disease:

               -  Nondilated (restrictive); or

               -  Hypertrophic cardiomyopathy; or

               -  Significant systemic ventricular outflow obstruction

          -  Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or
             implantable device

          -  Significant conduction defects (i.e. second or third degree atrio-ventricular block or
             sick sinus syndrome)

          -  Bradycardia: heart rate < 50 beats per minute (BPM)

          -  Use of an investigational drug or beta adrenergic blockers, including metoprolol,
             sotalol, within 30 days of enrollment

          -  History of drug sensitivity or allergic reaction to alpha or beta-blockers

          -  Low resting systolic blood pressure: < 90 mmHg

          -  Use of any other blood pressure lowering medication for treatment of hypertension
             within 30 days of enrollment except calcium channel blockers and diuretics

          -  History or current clinical evidence of moderate-to-severe obstructive pulmonary
             disease or reactive airway diseases (i.e. asthma) requiring therapy

          -  Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times
             upper limit of institutional normal

          -  Gastrointestinal, or biliary disorders that could impair absorption, metabolism, or
             excretion of orally administered medications

          -  Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or
             hypothyroidism) not controlled with medication

          -  Uncontrolled diabetes (controlled diabetes per the American Diabetes Association and
             International Diabetes Center's Glycemic Target Goals is hemoglobin A1C < 7%)

          -  Anemia (hematocrit < 28%)

          -  Currently using select CYP2D6 inhibitor or inducer medications

          -  Inability to swallow pills

          -  Female patients who are pregnant are not eligible; women of childbearing potential
             require a negative pregnancy test prior to starting study drug

          -  Lactating females are not eligible unless they have agreed to not breastfeed their
             infants

          -  Sexually active female patients of reproductive potential are not eligible unless they
             agree to use an effective contraceptive method during study and for 2 months after
             stopping the study drug; abstinence is an acceptable method of birth control

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met