Cardiac ToxicityPhase 3NCT00003070
Enalapril in Treating Heart Damage Patients Who Received Anthracycline Chemotherapy for Childhood Cancer
A Phase 3 study testing enalapril maleate and quality-of-life assessment in people with Cardiac Toxicity and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 61 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Cardiac Toxicity, Unspecified Childhood Solid Tumor, Protocol Specific
- What is being tested?
- enalapril maleate and quality-of-life assessment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 61 sitesin 3 countries
- Study dates
- Sep 2000to Mar 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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 locations and contacts
61 sites in 3 countries.
61 sites in 3 countries
United States55 sites
Mission Saint Joseph's Health System
Asheville, North Carolina, 28801
Emory University Hospital - Atlanta
Atlanta, Georgia, 30322
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, 21201
Johns Hopkins Oncology Center
Baltimore, Maryland, 21231-2410
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, 35294-3300
Boston Floating Hospital Infants and Children
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Medical University of South Carolina
Charleston, South Carolina, 29425-0721
Carolinas Medical Center
Charlotte, North Carolina, 28232-2861
Presbyterian Healthcare
Charlotte, North Carolina, 28233-3549
Children's Memorial Hospital, Chicago
Chicago, Illinois, 60614
Simmons Cancer Center - Dallas
Dallas, Texas, 75235-9154
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Shands Hospital and Clinics, University of Florida
Gainesville, Florida, 32610-100277
East Carolina University School of Medicine
Greenville, North Carolina, 27858-4354
Children's Hospital of Greenville Hospital System
Greenville, South Carolina, 29605
CCOP - Northern New Jersey
Hackensack, New Jersey, 07601
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
Baylor College of Medicine
Houston, Texas, 77030
University of Mississippi Medical Center
Jackson, Mississippi, 39216-4505
University of Kansas Medical Center
Kansas City, Kansas, 66160-7357
University of California San Diego Cancer Center
La Jolla, California, 92093-0658
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794
Sylvester Cancer Center, University of Miami
Miami, Florida, 33136
Miami Children's Hospital
Miami, Florida, 33155
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
MBCCOP - Gulf Coast
Mobile, Alabama, 36688
Yale Comprehensive Cancer Center
New Haven, Connecticut, 06520-8028
Schneider Children's Hospital
New Hyde Park, New York, 11042
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112
CCOP - Ochsner
New Orleans, Louisiana, 70121
Ochsner Clinic
New Orleans, Louisiana, 70121
Mount Sinai School of Medicine
New York, New York, 10029
Oklahoma Memorial Hospital
Oklahoma City, Oklahoma, 73126-0307
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, 94304
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134-1095
CCOP - Columbia River Program
Portland, Oregon, 97213
Naval Medical Center, Portsmouth
Portsmouth, Virginia, 23708-2197
Massey Cancer Center
Richmond, Virginia, 23298-0037
University of Rochester Cancer Center
Rochester, New York, 14642
University of California Davis Medical Center
Sacramento, California, 95817
MBCCOP - South Texas Pediatric
San Antonio, Texas, 78229-3900
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78284-7811
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
State University of New York - Upstate Medical University
Syracuse, New York, 13210
CCOP - Florida Pediatric
Tampa, Florida, 33682-7757
Walter Reed Army Medical Center
Washington D.C., District of Columbia, 20307-5000
CCOP - Wichita
Wichita, Kansas, 67214-3882
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, 27157-1082
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655
Canada5 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Children's Hospital
Hamilton, Ontario, L8N 3Z5
Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: Afterload Reduction Therapy for Late Anthracycline Cardiotoxicity: A Pediatric Oncology Group Cancer Control Study
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.
Read the 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.
- Being tested
- enalapril maleate, quality-of-life assessment
- Keywords
- unspecified childhood solid tumor, protocol specific, cardiac toxicity
- Medical subject headings
- Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enalapril maleateDrug
quality-of-life assessmentProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1 < 350/mg/m2 anthracycline dose | Experimental | < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 2 < 350mg/m2 anthracycline dose | Experimental | < 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 3 < 350mg/m2 anthracycline dose | Experimental | >= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 4 < 350mg/m2 anthracycline dose | Experimental | >= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 5 >= 350mg/m2 anthracycline dose | Experimental | < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 6 >=350mg/m2 anthracycline dose | Experimental | < 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 7 >= 350mg/m2 anthracycline dose | Experimental | >= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
| Stratum 8 >= 350mg/m2 anthracycline dose | Experimental | >= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment Receives: Drug: enalapril maleate; Procedure: quality-of-life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, two and five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2004 (estimated)
- Study startSep 2000
- Primary completionJul 2003
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac ToxicityStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Stephen Lipshultz, MD, Study chair, James P. Wilmot Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003070
- Sponsor's protocol ID
- P9480
- Other IDs
- POG-9480, NCI-P97-0086, CDR0000065745
- Status last verified
- Aug 2014
- First submitted
- 1 Nov 1999
- Last updated
- 5 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 9193351
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Afterload Reduction Therapy for Late Anthracycline Cardiotoxicity: A Pediatric Oncology Group Cancer Control Study
- ClinicalTrials.gov ID
- NCT00003070
- Acronym / sponsor ID
- P9480
- Keywords
- unspecified childhood solid tumor, protocol specific, cardiac toxicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2000
- Primary completion
- Jul 2003 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 1 Mar 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Stratum 1 < 350/mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment |
| Stratum 2 < 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment< 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment |
| Stratum 3 < 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment>= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment |
| Stratum 4 < 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment>= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment |
| Stratum 5 >= 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment |
| Stratum 6 >=350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment< 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment |
| Stratum 7 >= 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment>= 4 years of age at diagnosis < 4 years since cessation of anthracycline treatment |
| Stratum 8 >= 350mg/m2 anthracycline dose | Experimental | Drug: enalapril maleate, Procedure: quality-of-life assessment>= 4 years of age at diagnosis >= 4 years since cessation of anthracycline treatment |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enalapril maleate | Drug | 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 |
| quality-of-life assessment | Procedure or surgery | 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 |
Primary outcome
Cardiac functional status and quality of life
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2014.
- Background: PubMed 9193351Krischer 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Lipshultz, MD study chair
James P. Wilmot Cancer Center
61 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing enalapril maleate and quality-of-life assessment in people with Cardiac Toxicity and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 61 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States, Canada, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac functional status and quality of life (time frame: baseline, two and five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00003070, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2014.