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

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003070

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

77.9

Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Toxicity Unspecified Childhood Solid Tumor, Protocol Specific	Drug: enalapril maleate Procedure: quality-of-life assessment	Phase 3

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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Sep 1, 2000

Actual Primary Completion Date :

Jul 1, 2003

Actual Study Completion Date :

Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum 1 < 350/mg/m2 anthracycline dose < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 2 < 350mg/m2 anthracycline dose < 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 3 < 350mg/m2 anthracycline dose >= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 4 < 350mg/m2 anthracycline dose >= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 5 >= 350mg/m2 anthracycline dose < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 6 >=350mg/m2 anthracycline dose < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 7 >= 350mg/m2 anthracycline dose >= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment
Experimental: Stratum 8 >= 350mg/m2 anthracycline dose >= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment	Drug: enalapril maleate Procedure: quality-of-life assessment

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36688
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
5	Lucile Packard Children's Hospital at Stanford	Palo Alto	California	United States	94304
6	University of California Davis Medical Center	Sacramento	California	United States	95817
7	Yale Comprehensive Cancer Center	New Haven	Connecticut	United States	06520-8028
8	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
9	Shands Hospital and Clinics, University of Florida	Gainesville	Florida	United States	32610-100277
10	Sylvester Cancer Center, University of Miami	Miami	Florida	United States	33136
11	Miami Children's Hospital	Miami	Florida	United States	33155
12	CCOP - Florida Pediatric	Tampa	Florida	United States	33682-7757
13	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
14	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
15	Children's Memorial Hospital, Chicago	Chicago	Illinois	United States	60614
16	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
17	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
18	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
19	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
20	Ochsner Clinic	New Orleans	Louisiana	United States	70121
21	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
22	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21231-2410
23	Boston Floating Hospital Infants and Children	Boston	Massachusetts	United States	02111
24	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
25	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
26	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
27	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
28	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
29	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
30	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
31	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
32	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
33	Schneider Children's Hospital	New Hyde Park	New York	United States	11042
34	Mount Sinai School of Medicine	New York	New York	United States	10029
35	University of Rochester Cancer Center	Rochester	New York	United States	14642
36	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
37	Mission Saint Joseph's Health System	Asheville	North Carolina	United States	28801
38	Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
39	Presbyterian Healthcare	Charlotte	North Carolina	United States	28233-3549
40	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
41	East Carolina University School of Medicine	Greenville	North Carolina	United States	27858-4354
42	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
43	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma	United States	73126-0307
44	CCOP - Columbia River Program	Portland	Oregon	United States	97213
45	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
46	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
47	Children's Hospital of Greenville Hospital System	Greenville	South Carolina	United States	29605
48	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
49	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
50	Baylor College of Medicine	Houston	Texas	United States	77030
51	MBCCOP - South Texas Pediatric	San Antonio	Texas	United States	78229-3900
52	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
53	Naval Medical Center, Portsmouth	Portsmouth	Virginia	United States	23708-2197
54	Massey Cancer Center	Richmond	Virginia	United States	23298-0037
55	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
56	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
57	Children's Hospital	Hamilton	Ontario	Canada	L8N 3Z5
58	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
59	Montreal Children's Hospital	Montreal	Quebec	Canada	H3H 1P3
60	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
61	Swiss Pediatric Oncology Group Bern	Bern		Switzerland	CH 3010