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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003070
First received: November 1, 1999
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Supportive Care
Official Title: Afterload Reduction Therapy for Late Anthracycline Cardiotoxicity: A Pediatric Oncology Group Cancer Control Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Cardiac functional status and quality of life [ Time Frame: baseline, two and five years ] [ Designated as safety issue: No ]
    Cardiac functional status (depressed fractional shortening) and quality-of-life, will be assessed at baseline, two and five years into the study.


Enrollment: 13
Study Start Date: September 2000
Study Completion Date: March 2007
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003070

  Show 61 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Stephen Lipshultz, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003070     History of Changes
Other Study ID Numbers: P9480, POG-9480, NCI-P97-0086, CDR0000065745
Study First Received: November 1, 1999
Last Updated: August 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
unspecified childhood solid tumor, protocol specific
cardiac toxicity

Additional relevant MeSH terms:
Enalapril
Enalaprilat
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014