Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This randomized phase II trial studies the side effects and how well low-dose carvedilol works in preventing congestive heart failure (CHF) in younger cancer survivors exposed to high dose anthracyclines for management of childhood cancer. Carvedilol may help lower the risk of cardiovascular complications

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Carvedilol

Criteria

Inclusion Criteria:

• Cancer diagnosis prior to 22 years of age, irrespective of current age

• Lifetime cumulative anthracycline dose: >= 300 mg/m^2 without the protection of dexrazoxane (Zinecard) therapy

• Time from completion of cancer treatment to study entry: >= 2 years

Exclusion Criteria:

• Receiving treatment for cardiomyopathy or congestive heart failure

• Resting ejection fraction < 50% or fractional shortening < 25%

• Uncorrected primary obstructive or severe regurgitative valvular disease, nondilated (restrictive) or hypertrophic cardiomyopathy, or significant systemic ventricular outflow obstruction

• Low resting systolic blood pressure: < 90 mm hemoglobin (Hg)

• Bradycardia: heart rate < 50 beats per minute (BPM)

• 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)

• History or current clinical evidence of moderate -to-severe obstructive pulmonary disease or reactive airway diseases (i.e.: asthma) requiring therapy

• Significant hepatic (serum aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] > 3 time upper limit of normal 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, or insulin dependent diabetes mellitus

• Females of child bearing potential who are pregnant, lactating, or sexually active and not taking adequate contraceptive precautions (i.e.: intrauterine device [IUD] or oral contraceptives for 3 months prior to entry into the study)

• History of drug sensitivity or allergic reaction to alpha- or beta-blockers

• Anemia (hematocrit < 28%)

• Use of an investigational drug or beta adrenergic blockers, including metoprolol, sotalol, within 30 days of randomization

• Use of select cytochrome P450 2D6 (CYP2D6) inhibitor medications

• Inability to swallow pills

• Unwillingness or inability to cooperate, or, for the parents or guardians of minors, to give consent, or for the child to give assent, or any condition of sufficient severity to impair cooperation with the study

• Use of any other blood pressure lowering medication for treatment of hypertension, within 30 days of randomization