Enalapril in Treating Heart Damage Patients Who Received Anthracycline Chemotherapy for Childhood Cancer

NCT00003070 | Completed Phase 3 DMC

• 4 other identifiers: P9480POG-9480NCI-P97-0086CDR0000065745
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 61

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as enalapril, may protect normal cells from the toxic effects of chemotherapy. It is not known whether enalapril is more effective than a placebo in treating heart damage in patients who received anthracycline chemotherapy for childhood cancer. PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of enalapril with a placebo in treating heart damage in patients who received anthracycline chemotherapy for childhood cancer.

Conditions

Cardiac Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

unspecified childhood solid tumor, protocol specific; cardiac toxicity

Outcome Measures

Primary Outcomes (1)

• Cardiac functional status and quality of life

  Cardiac functional status (depressed fractional shortening) and quality-of-life, will be assessed at baseline, two and five years into the study.

  baseline, two and five years

Study Arms (8)

Stratum 1 < 350/mg/m2 anthracycline dose

EXPERIMENTAL

\< 4 years of age at diagnosis \< 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 2 < 350mg/m2 anthracycline dose

EXPERIMENTAL

\< 4 years of age at diagnosis \>= 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 3 < 350mg/m2 anthracycline dose

EXPERIMENTAL

\>= 4 years of age at diagnosis \< 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 4 < 350mg/m2 anthracycline dose

EXPERIMENTAL

\>= 4 years of age at diagnosis \>= 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 5 >= 350mg/m2 anthracycline dose

EXPERIMENTAL

\< 4 years of age at diagnosis \< 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 6 >=350mg/m2 anthracycline dose

EXPERIMENTAL

\< 4 years of age at diagnosis \< 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 7 >= 350mg/m2 anthracycline dose

EXPERIMENTAL

\>= 4 years of age at diagnosis \< 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Stratum 8 >= 350mg/m2 anthracycline dose

EXPERIMENTAL

\>= 4 years of age at diagnosis \>= 4 years since cessation of anthracycline treatment

Drug: enalapril maleate; Procedure: quality-of-life assessment

Interventions

enalapril maleate DRUG

Stratum 1 < 350/mg/m2 anthracycline dose; Stratum 2 < 350mg/m2 anthracycline dose; Stratum 3 < 350mg/m2 anthracycline dose; Stratum 4 < 350mg/m2 anthracycline dose; Stratum 5 >= 350mg/m2 anthracycline dose; Stratum 6 >=350mg/m2 anthracycline dose; Stratum 7 >= 350mg/m2 anthracycline dose; Stratum 8 >= 350mg/m2 anthracycline dose

quality-of-life assessment PROCEDURE

Stratum 1 < 350/mg/m2 anthracycline dose; Stratum 2 < 350mg/m2 anthracycline dose; Stratum 3 < 350mg/m2 anthracycline dose; Stratum 4 < 350mg/m2 anthracycline dose; Stratum 5 >= 350mg/m2 anthracycline dose; Stratum 6 >=350mg/m2 anthracycline dose; Stratum 7 >= 350mg/m2 anthracycline dose; Stratum 8 >= 350mg/m2 anthracycline dose

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Histologically diagnosed childhood malignancy that had prior anthracycline therapy Echocardiographic evidence of reduced fractional shortening, reduced contractility, or increased afterload, or any combination At least 6 months oncologic disease free PATIENT CHARACTERISTICS: Age: At least 8 at study entry and less than 22 at diagnosis Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: No history of renal disease No known renal artery stenosis Cardiovascular: No congenital cardiovascular malformations No active congestive heart failure not attributable to sepsis or renal failure No medication for heart condition No history of symptomatic arrhythmia antedating anthracycline therapy No constrictive pericarditis No uncontrolled hypertension Pulmonary: No primary valvular or outflow tract obstruction Other: Not pregnant or lactating Must use adequate contraception No reaction or intolerance to ACE inhibitors PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 1 year since prior cumulative anthracycline therapy of at least 200 mg/m2 No prior amsacrine therapy Endocrine therapy: Not specified Radiotherapy: No prior mediastinal, spinal, or total body irradiation that included the heart Surgery: Not specified Other: No concurrent angiotensin converting enzyme (ACE)inhibitor treatment No concurrent treatment with other investigational drug No oncologic therapy within past 6 months

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (61)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294-3300, United States

Location

MBCCOP - Gulf Coast

Mobile, Alabama, 36688, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Yale Comprehensive Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5000, United States

Location

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, 32610-100277, United States

Location

Sylvester Cancer Center, University of Miami

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

CCOP - Florida Pediatric

Tampa, Florida, 33682-7757, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Children's Memorial Hospital, Chicago

Chicago, Illinois, 60614, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Ochsner Clinic

New Orleans, Louisiana, 70121, United States

Location

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231-2410, United States

Location

Boston Floating Hospital Infants and Children

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

CCOP - Northern New Jersey

Hackensack, New Jersey, 07601, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11042, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Rochester Cancer Center

Rochester, New York, 14642, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Mission Saint Joseph's Health System

Asheville, North Carolina, 28801, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Healthcare

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

East Carolina University School of Medicine

Greenville, North Carolina, 27858-4354, United States

Location

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

Oklahoma Memorial Hospital

Oklahoma City, Oklahoma, 73126-0307, United States

Location

CCOP - Columbia River Program

Portland, Oregon, 97213, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

Children's Hospital of Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105-2794, United States

Location

Simmons Cancer Center - Dallas

Dallas, Texas, 75235-9154, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MBCCOP - South Texas Pediatric

San Antonio, Texas, 78229-3900, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Naval Medical Center, Portsmouth

Portsmouth, Virginia, 23708-2197, United States

Location

Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Swiss Pediatric Oncology Group Bern

Bern, CH 3010, Switzerland

Location

Related Publications (1)

• Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. J Clin Oncol. 1997 Apr;15(4):1544-52. doi: 10.1200/JCO.1997.15.4.1544.

  PMID: 9193351 BACKGROUND

MeSH Terms

Conditions

Cardiotoxicity

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Stephen Lipshultz, MD

  James P. Wilmot Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: March 1, 2004
• Study Start: September 1, 2000
• Primary Completion: July 1, 2003
• Study Completion: March 1, 2007
• Last Updated: August 5, 2014

Record last verified: 2014-08

Locations

CA (5); CH (1); US (55)