Purpose

This randomized 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.

Condition

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm I (carvedilol)
Patients receive low-dose carvedilol PO QD or BID for 24 months.
  • Drug: Carvedilol
    Given PO
    Other names:
    • Coreg
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacogenomic Study
    Correlative studies
    Other names:
    • PHARMACOGENOMIC
  • Other: Pharmacological Study
    Correlative studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other names:
    • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Placebo Comparator
Arm II (placebo)
Patients receive placebo PO QD or BID for 24 months.
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacogenomic Study
    Correlative studies
    Other names:
    • PHARMACOGENOMIC
  • Other: Pharmacological Study
    Correlative studies
  • Other: Placebo
    Given PO
    Other names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other names:
    • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Site Public Contact
202-884-2549

More Details

NCT ID
NCT02717507
Status
Recruiting
Sponsor
Children's Oncology Group

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of heart failure (HF) risk, including: Left ventricular (LV) posterior wall thickness-dimension ratio (LV T-D); LV systolic and diastolic function, and afterload; Natriuretic peptides, troponins, and galectin-3.

SECONDARY OBJECTIVES:

I. To establish safety and tolerability of this two-year course of low-dose carvedilol, assessing both objective measures (hepatic function) and patient reported outcomes.

II. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year carvedilol intervention.

TERTIARY OBJECTIVES:

I. To evaluate the long-term efficacy of carvedilol in preventing cardiomyopathy and/or heart failure in high-risk childhood cancer survivors.

OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months.

ARM II: Patients receive placebo PO QD or BID for 24 months.

After completion of study treatment, patients are followed up for 3 years.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.