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.

Condition	Treatment or Intervention	Phase
cardiac toxicity unspecified childhood solid tumor, protocol specific	Drug: enalapril	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  8 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36688,  United States
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      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
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8028,  United States
District of Columbia
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      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
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      Children's Memorial Hospital, Chicago, Chicago,  Illinois,  60614,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Louisiana
      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
Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231-2410,  United States
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      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
Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      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
North Carolina
      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
      Oklahoma Memorial Hospital, Oklahoma City,  Oklahoma,  73126-0307,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
Pennsylvania
      St. Christopher's Hospital for Children, Philadelphia,  Pennsylvania,  19134-1095,  United States
South Carolina
      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
Tennessee
      Saint Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
Texas
      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
Virginia
      Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Naval Medical Center, Portsmouth, Portsmouth,  Virginia,  23708-2197,  United States
Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, Ontario
      Children's Hospital, Hamilton,  Ontario,  L8N 3Z5,  Canada
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada
Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada
      Montreal Children's Hospital, Montreal,  Quebec,  H3H 1P3,  Canada
Switzerland
      Swiss Pediatric Oncology Group Bern, Bern,  CH 3010,  Switzerland

Study chairs or principal investigators

Stephen Lipshultz,  Study Chair,  Pediatric Oncology Group   

Study ID Numbers:  CDR0000065745; POG-9480; NCI-P97-0086
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003070
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08