Overview

This trial is active, not recruiting.

Condition cancer survivor
Treatments carvedilol, placebo, pharmacogenomic studies, laboratory biomarker analysis, quality-of-life assessment, polymorphism analysis, microarray analysis, polymerase chain reaction, enzyme-linked immunosorbent assay, questionnaire administration
Phase phase 2
Sponsor City of Hope Medical Center
Collaborator National Cancer Institute (NCI)
Start date May 2012
End date June 2017
Trial size 250 participants
Trial identifier NCT01347970, 11018, K12CA001727, NCI-2011-00717

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose supportive care
Arm
(Experimental)
Patients receive low-dose carvedilol PO QD or BID for 24 months.
carvedilol Coreg
Given PO
pharmacogenomic studies Pharmacogenomic Study
Correlative studies
laboratory biomarker analysis
Correlative studies
quality-of-life assessment quality of life assessment
Ancillary studies
polymorphism analysis
Correlative studies
microarray analysis gene expression profiling
Correlative studies
polymerase chain reaction PCR
Correlative studies
enzyme-linked immunosorbent assay ELISA
Correlative studies
questionnaire administration
Ancillary studies
(Placebo Comparator)
Patients receive placebo PO QD or BID for 24 months.
placebo PLCB
Given PO
pharmacogenomic studies Pharmacogenomic Study
Correlative studies
laboratory biomarker analysis
Correlative studies
quality-of-life assessment quality of life assessment
Ancillary studies
polymorphism analysis
Correlative studies
microarray analysis gene expression profiling
Correlative studies
polymerase chain reaction PCR
Correlative studies
enzyme-linked immunosorbent assay ELISA
Correlative studies
questionnaire administration
Ancillary studies

Primary Outcomes

Measure
LV thickness-dimension ratio (LV T-D), reported in terms of LV posterior wall dimension in systole and LV dimension based on the internal diameter in diastole
time frame: Up to 24 months

Secondary Outcomes

Measure
Echocardiographic efficacy measures, including afterload and systolic and diastolic measurements
time frame: Up to 24 months
Blood biomarkers of myocardial remodeling and CHF risk, including cardiac troponins (cTn), blood natriuretic peptide (BNP), and galectin-3
time frame: Up to 24 months
Grade 2-4 toxicities, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: Up to 24 months
Frequency of individuals with elevated liver function measurements (bilirubin, AST, ALT)
time frame: Up to 24 months
Subjective safety and tolerability measures, including treatment adherence as measured by pill counts and patient reported symptoms
time frame: Up to 24 months

Eligibility Criteria

Male or female participants at least 16 years old.

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

Additional Information

Official title Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial
Principal investigator Saro Armenian, DO, MPH
Description PRIMARY OBJECTIVES: I. To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of CHF risk, including: left ventricular (LV) posterior wall thickness-dimension ratio (LV T-D); LV systolic and diastolic function, and afterload; natriuretic peptides, troponins, and galactin-3. II. To establish safety and tolerability of this two-year course of low-dose carvedilol, assessing both objective measures (hepatic function) and patients reported outcomes. III. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year carvedilol intervention. IV. As an exploratory goal, to examine the relationship between carvedilol and clinical measures of efficacy such as prevention of CHF. SECONDARY OBJECTIVES: I. 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 (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 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by City of Hope Medical Center.
Location data was received from the National Cancer Institute and was last updated in August 2016.