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

Primary Purpose

Cardiac Toxicity, Unspecified Childhood Solid Tumor, Protocol Specific

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
enalapril maleate
quality-of-life assessment
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cardiac Toxicity focused on measuring unspecified childhood solid tumor, protocol specific, cardiac toxicity

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham Comprehensive Cancer Center
  • MBCCOP - Gulf Coast
  • University of Arkansas for Medical Sciences
  • University of California San Diego Cancer Center
  • Lucile Packard Children's Hospital at Stanford
  • University of California Davis Medical Center
  • Yale Comprehensive Cancer Center
  • Walter Reed Army Medical Center
  • Shands Hospital and Clinics, University of Florida
  • Sylvester Cancer Center, University of Miami
  • Miami Children's Hospital
  • CCOP - Florida Pediatric
  • Emory University Hospital - Atlanta
  • Cancer Research Center of Hawaii
  • Children's Memorial Hospital, Chicago
  • University of Kansas Medical Center
  • CCOP - Wichita
  • MBCCOP - LSU Health Sciences Center
  • CCOP - Ochsner
  • Ochsner Clinic
  • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Johns Hopkins Oncology Center
  • Boston Floating Hospital Infants and Children
  • Dana-Farber Cancer Institute
  • University of Massachusetts Memorial Medical Center
  • Children's Hospital of Michigan
  • University of Mississippi Medical Center
  • Cardinal Glennon Children's Hospital
  • Washington University School of Medicine
  • CCOP - Northern New Jersey
  • Hackensack University Medical Center
  • Roswell Park Cancer Institute
  • Schneider Children's Hospital
  • Mount Sinai School of Medicine
  • University of Rochester Cancer Center
  • State University of New York - Upstate Medical University
  • Mission Saint Joseph's Health System
  • Carolinas Medical Center
  • Presbyterian Healthcare
  • Duke Comprehensive Cancer Center
  • East Carolina University School of Medicine
  • Comprehensive Cancer Center at Wake Forest University
  • Oklahoma Memorial Hospital
  • CCOP - Columbia River Program
  • St. Christopher's Hospital for Children
  • Medical University of South Carolina
  • Children's Hospital of Greenville Hospital System
  • Saint Jude Children's Research Hospital
  • Simmons Cancer Center - Dallas
  • Baylor College of Medicine
  • MBCCOP - South Texas Pediatric
  • University of Texas Health Science Center at San Antonio
  • Naval Medical Center, Portsmouth
  • Massey Cancer Center
  • Midwest Children's Cancer Center
  • Cross Cancer Institute
  • Children's Hospital
  • Hospital for Sick Children
  • Montreal Children's Hospital
  • Hopital Sainte Justine
  • Swiss Pediatric Oncology Group Bern

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Arm Description

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
August 4, 2014
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003070
Brief Title
Enalapril in Treating Heart Damage 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 Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
September 2000 (undefined)
Primary Completion Date
July 2003 (Actual)
Study Completion Date
March 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Toxicity, Unspecified Childhood Solid Tumor, Protocol Specific
Keywords
unspecified childhood solid tumor, protocol specific, cardiac toxicity

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
Double
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stratum 1 < 350/mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment
Arm Title
Stratum 2 < 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
< 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment
Arm Title
Stratum 3 < 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
>= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment
Arm Title
Stratum 4 < 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
>= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment
Arm Title
Stratum 5 >= 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment
Arm Title
Stratum 6 >=350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment
Arm Title
Stratum 7 >= 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
>= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment
Arm Title
Stratum 8 >= 350mg/m2 anthracycline dose
Arm Type
Experimental
Arm Description
>= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment
Intervention Type
Drug
Intervention Name(s)
enalapril maleate
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Primary Outcome Measure Information:
Title
Cardiac functional status and quality of life
Description
Cardiac functional status (depressed fractional shortening) and quality-of-life, will be assessed at baseline, two and five years into the study.
Time Frame
baseline, two and five years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Lipshultz, MD
Organizational Affiliation
James P. Wilmot Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
MBCCOP - Gulf Coast
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36688
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Lucile Packard Children's Hospital at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Yale Comprehensive Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8028
Country
United States
Facility Name
Walter Reed Army Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20307-5000
Country
United States
Facility Name
Shands Hospital and Clinics, University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-100277
Country
United States
Facility Name
Sylvester Cancer Center, University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
CCOP - Florida Pediatric
City
Tampa
State/Province
Florida
ZIP/Postal Code
33682-7757
Country
United States
Facility Name
Emory University Hospital - Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Cancer Research Center of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Children's Memorial Hospital, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3882
Country
United States
Facility Name
MBCCOP - LSU Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
CCOP - Ochsner
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Ochsner Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
Facility Name
Boston Floating Hospital Infants and Children
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
CCOP - Northern New Jersey
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Schneider Children's Hospital
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Rochester Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Mission Saint Joseph's Health System
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28232-2861
Country
United States
Facility Name
Presbyterian Healthcare
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28233-3549
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
East Carolina University School of Medicine
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858-4354
Country
United States
Facility Name
Comprehensive Cancer Center at Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1082
Country
United States
Facility Name
Oklahoma Memorial Hospital
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73126-0307
Country
United States
Facility Name
CCOP - Columbia River Program
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134-1095
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0721
Country
United States
Facility Name
Children's Hospital of Greenville Hospital System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-2794
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
MBCCOP - South Texas Pediatric
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
Naval Medical Center, Portsmouth
City
Portsmouth
State/Province
Virginia
ZIP/Postal Code
23708-2197
Country
United States
Facility Name
Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Hopital Sainte Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Swiss Pediatric Oncology Group Bern
City
Bern
ZIP/Postal Code
CH 3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
9193351
Citation
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.
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Enalapril in Treating Heart Damage Patients Who Received Anthracycline Chemotherapy for Childhood Cancer

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