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

Condition(s) targeted: Cardiac Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: enalapril maleate (Drug); quality-of-life assessment (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: Pediatric Oncology Group

Official(s) and/or principal investigator(s):
Stephen Lipshultz, MD, Study Chair, Affiliation: James P. Wilmot Cancer Center

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.

Official title: Afterload Reduction Therapy for Late Anthracycline Cardiotoxicity: A Pediatric Oncology Group Cancer Control Study

Study design: Supportive Care, Randomized, Double-Blind, Placebo Control

Detailed description: OBJECTIVES: I. Determine whether enalapril treatment results in a reduction in body surface area-adjusted left ventricular mass in anthracycline-treated survivors of childhood cancer. II. Determine whether improvement in ventricular function achieved by enalapril is sustained and alters the course of late cardiotoxicity. III. Determine the impact of enalapril therapy on quality of life.

OUTLINE: This is a double blind, placebo controlled, randomized study. Patients are stratified based on the cumulative anthracycline dose, age at cancer diagnosis, and the duration of time since cessation of anthracycline therapy. Patients are administered enalapril or placebo by mouth bid. Patients undergo a series of cardiac tests after administration of drug. Follow-up occurs at 2, 6, and 12 months and every year thereafter.

PROJECTED ACCRUAL: 75 patients in each treatment arm will be accrued.

Minimum age: 8 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Swiss Pediatric Oncology Group Bern, Bern CH 3010, Switzerland

MBCCOP - Gulf Coast, Mobile, Alabama 36688, United States

University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, United States

Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Lucile Packard Children's Hospital at Stanford, Palo Alto, California 94304, United States

University of California Davis Medical Center, Sacramento, California 95817, United States

University of California San Diego Cancer Center, La Jolla, California 92093-0658, United States

Yale Comprehensive Cancer Center, New Haven, Connecticut 06520-8028, United States

Walter Reed Army Medical Center, Washington, District of Columbia 20307-5000, United States

CCOP - Florida Pediatric, Tampa, Florida 33682-7757, United States

Miami Children's Hospital, Miami, Florida 33155, United States

Shands Hospital and Clinics, University of Florida, Gainesville, Florida 32610-100277, United States

Sylvester Cancer Center, University of Miami, Miami, Florida 33136, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

Children's Memorial Hospital, Chicago, Chicago, Illinois 60614, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

CCOP - Ochsner, New Orleans, Louisiana 70121, United States

MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States

Ochsner Clinic, New Orleans, Louisiana 70121, United States

Johns Hopkins Oncology Center, Baltimore, Maryland 21231-2410, United States

Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, United States

Boston Floating Hospital Infants and Children, Boston, Massachusetts 02111, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States

Washington University School of Medicine, Saint Louis, Missouri 63110, United States

CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Mount Sinai School of Medicine, New York, New York 10029, United States

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

Schneider Children's Hospital, New Hyde Park, New York 11042, United States

State University of New York - Upstate Medical University, Syracuse, New York 13210, United States

University of Rochester Cancer Center, Rochester, New York 14642, United States

Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, United States

Mission Saint Joseph's Health System, Asheville, North Carolina 28801, United States

Presbyterian Healthcare, Charlotte, North Carolina 28233-3549, United States

Oklahoma Memorial Hospital, Oklahoma City, Oklahoma 73126-0307, United States

Children's Hospital, Hamilton, Ontario L8N 3Z5, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

CCOP - Columbia River Program, Portland, Oregon 97213, United States

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada

Children's Hospital of Greenville Hospital System, Greenville, South Carolina 29605, United States

Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States

Saint Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, United States

Baylor College of Medicine, Houston, Texas 77030, United States

MBCCOP - South Texas Pediatric, San Antonio, Texas 78229-3900, United States

Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States

Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Naval Medical Center, Portsmouth, Portsmouth, Virginia 23708-2197, United States

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

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.

Starting date: August 1997
Last updated: May 23, 2008