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

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Cardiac Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Procedure: quality-of-life assessment; Drug: enalapril maleate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003070

NCI-P97-0086 (Other Identifier)

P9480

POG-9480 (Other Identifier)

CDR0000065745 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 8+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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13 participants in 8 patient groups

Stratum 1 < 350/mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 2 < 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 3 < 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 4 < 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 5 >= 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 6 >=350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 7 >= 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate

Stratum 8 >= 350mg/m2 anthracycline dose

Experimental group

Description:

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

Treatment:

Procedure: quality-of-life assessment

Drug: enalapril maleate