Protocol Summary

Protocol No.: OCR15112

Sponsor Protocol No.: ALTE1621

Study Title
Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Heart Failure (PREVENT-HF): A Phase 2b Randomized Placebo-Controlled (Carvedilol) Trial

Principal Investigator(s)
Slayton, William

Objective
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.

Phase: Phase II

Age Group: Both

Scope: National

Treatment
Arm I (carvedilol)
Patients receive low-dose carvedilol PO QD or BID for 24 months.

Arm II (placebo)
Patients receive placebo PO QD or BID for 24 months.

Detailed Eligibility
INCLUSION CRITERIA:
1. Males must weigh >55 Kg
2. Females must weigh >50 Kg
3. Patient must have had a cancer diagnosis 4. Patient must have a lifetime cumulative anthracycline dose: >= 300 mg/m^2 DOXOrubicin equivalent without the protection of dexrazoxane (zinecard) therapy
5. Patient must have completed cancer treatment >= 2 years prior to study enrollment

EXCLUSION CRITERIA:
1. Receiving treatment for cardiomyopathy or heart failure
2. Ejection fraction of 3. Shortening fraction of 4. Uncorrected primary obstructive or severe regurgitative valvular disease:
- Nondilated (restrictive); or
- Hypertrophic cardiomyopathy; or
- Significant systemic ventricular outflow obstruction
5. Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device
6. Significant conduction defects (i.e. second or third degree atrioventricular block or sick sinus syndrome)
7. Bradycardia: heart rate 8. Use of an investigational drug or beta adrenergic blockers, including metoprolol, sotalol, within 30 days of enrollment
9. History of drug sensitivity or allergic reaction to alpha or beta-blockers
10. Low resting systolic blood pressure: 11. Use of any other blood pressure lowering medication for treatment of hypertension within 30 days of enrollment except calcium channel blockers and diuretics
12. History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e. asthma) requiring therapy
13. Significant hepatic (serum aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] > 3 time upper limit of institutional normal)
14. Gastrointestinal, or biliary disorders that could impair absorption, metabolism, or excretion of orally administered medications
15. Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or hypothyroidism) not controlled with medication
16. Insulin dependent diabetes mellitus
17. Anemia (hematocrit 18. Use of select cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) inhibitor or inducer medications
19. Inability to swallow pills
20. Female patients who are pregnant are not eligible; women of childbearing potential require a negative pregnancy test prior to starting study drug
21. Lactating females are not eligible unless they have agreed to not breastfeed their infants
22. Sexually active 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
23. All patients and/or their parents or legal guardians must sign a written informed consent
24. All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Applicable Disease Sites
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville