Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors

NCT ID: NCT02717507

Last Updated: 2025-04-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

196 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-04

Study Completion Date

2025-03-31

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

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.

EXPLORATORY OBJECTIVE:

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.

Conditions

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Hematopoietic and Lymphoid Cell Neoplasm Malignant Solid Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm I (carvedilol)

Patients receive low-dose carvedilol PO QD or BID for 24 months.

Group Type EXPERIMENTAL

Carvedilol

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacogenomic Study

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Arm II (placebo)

Patients receive placebo PO QD or BID for 24 months.

Group Type PLACEBO_COMPARATOR

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacogenomic Study

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Placebo Administration

Intervention Type OTHER

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Carvedilol

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacogenomic Study

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Placebo Administration

Given PO

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Coreg PHARMACOGENOMIC Quality of Life Assessment

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Saro H Armenian

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, United States

Site Status

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

El Paso Children's Hospital

El Paso, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Perth Children's Hospital

Perth, Western Australia, Australia

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

Starship Children's Hospital

Grafton, Auckland, New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Countries

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United States Australia Canada New Zealand

References

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Armenian SH, Hudson MM, Chen MH, Colan SD, Lindenfeld L, Mills G, Siyahian A, Gelehrter S, Dang H, Hein W, Green DM, Robison LL, Wong FL, Douglas PS, Bhatia S. Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure. BMC Cardiovasc Disord. 2016 Oct 4;16(1):187. doi: 10.1186/s12872-016-0364-6.

Reference Type DERIVED
PMID: 27716152 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://clinicaltrials.gov/ct2/show/NCT01347970?term=NCT01347970&draw=2&rank=1

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

Other Identifiers

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NCI-2016-00232

Identifier Type: REGISTRY

Identifier Source: secondary_id

ALTE1621

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ALTE1621

Identifier Type: OTHER

Identifier Source: secondary_id

ALTE1621

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA196854

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189955

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ALTE1621

Identifier Type: -

Identifier Source: org_study_id

NCT01347970

Identifier Type: -

Identifier Source: nct_alias

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