The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01790152




Registration number
NCT01790152
Ethics application status
Date submitted
11/02/2013
Date registered
13/02/2013
Date last updated
8/11/2019

Titles & IDs
Public title
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
Scientific title
Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy
Secondary ID [1] 0 0
NCI-2012-03196
Secondary ID [2] 0 0
ALTE11C2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma in Remission 0 0
Leukemia in Remission 0 0
Lymphoblastic Lymphoma 0 0
Osteosarcoma 0 0
Recurrent Leukemia 0 0
Recurrent Lymphoma 0 0
Recurrent Malignant Neoplasm 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Children's - Other
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Other interventions - Assessment of Therapy Complications
Other interventions - Laboratory Biomarker Analysis
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration

Ancillary-Correlative (laboratory biomarker analysis) - Patients complete a diagnostic symptom checklist, undergo a physical exam, echocardiogram, collection of serum for biomarker testing, and a 6 minute walk test, and complete quality of life, family history, physical activity, and smoking questionnaires.


Other interventions: Assessment of Therapy Complications
Ancillary studies

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Left ventricular function and measures of pathologic remodeling (i.e., thickness-to-dimension ratio) assessed using standard 2-dimensional, M-mode, and Doppler echocardiogram - Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.
Timepoint [1] 0 0
Baseline
Primary outcome [2] 0 0
Differences in serum biomarkers (particularly cardiac troponins and natriuretic peptides) - Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.
Timepoint [2] 0 0
Baseline
Secondary outcome [1] 0 0
Quality of life based on self-report instruments - An analytic Markov model will be created and used. Estimates and their 95% confidence will be included to explore the sensitivity of any quality-adjusted life years estimates.
Timepoint [1] 0 0
Baseline
Secondary outcome [2] 0 0
Primary disease relapse - An analytic Markov model will be created and used.
Timepoint [2] 0 0
Baseline
Secondary outcome [3] 0 0
Second cancer rates - An analytic Markov model will be created and used.
Timepoint [3] 0 0
Baseline
Secondary outcome [4] 0 0
Longitudinal trajectory of 2-dimensional echocardiographic parameters - Will utilize generalized linear model-general estimation equation to model the trajectories of echocardiographic biomarker estimates (continuous outcomes) across time. Relevant model shapes will be evaluated, beginning with linear models, but also testing more flexible shapes (e.g., quadratic, cubic, or cubic spline functions with varying numbers of knots) to determine whether non-linear components are needed for fit. Will also examine interactions of dexrazoxane (DRZ) status with the selected functions of time to evaluate for differences in trajectories over time by DRZ status.
Timepoint [4] 0 0
From time of cancer treatment to subsequent follow-up

Eligibility
Key inclusion criteria
- STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS

- Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on
P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)

- STRATUM I: Alive and in continuous first complete remission from their original cancer
(leukemia/lymphoblastic lymphoma [P9404, high-risk DFCI 95-01] or Hodgkin lymphoma
[P9425/P9426])

- STRATUM I: Did not have progressive disease or induction failure requiring
off-protocol therapy including hematopoietic cell transplantation

- STRATUM I: Must not have been diagnosed with any subsequent malignancy that required
additional cardiotoxic therapies (i.e., radiotherapy to the chest [also includes
fields directed towards the neck, upper abdomen, or spine], or additional
anthracyclines or anthraquinones); patients with history of subsequent malignancy that
did not require such therapies remain eligible

- STRATUM I: All patients and/or their parents or legal guardians must sign a written
informed consent

- STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404,
P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have
experienced a subsequent malignancy that precludes eligibility since their original
diagnosis, the study committee will review the available data (both from Children's
Oncology Group's [COG?s] Statistics and Data Center [SDC] and the participating
institution) to determine if individual patients are to be selected for Stratum 2; in
recognition that local institutions sometimes have more updated relapse/subsequent
cancer data than SDC, in cases where local data is more updated, local data will be
used preferentially; the study will petition the Institutional Review Board (IRB)
specifically for a waiver of consent to include any relapse and subsequent cancer data
obtained from existing records for analysis of the secondary aims; patients selected
for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but
who lack clear confirmation in existing records (either at SDC or at the local
institution)

- STRATUM II: Alive, but have experienced relapse of their original cancer and/or have
developed a subsequent cancer (other than non-melanomatous skin cancer) since their
original diagnosis

- STRATUM II: All patients and/or their parents or legal guardians must sign a written
informed consent

- STRATUM III: OSTEOSARCOMA SURVIVORS

- Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able
(themselves and/or parents/legal guardian) to provide written informed consent; note
that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors

- Comparison subjects for P9754 survivors will be eligible to be enrolled from any
ALTE11C2 participating COG site (even if that institution did not participate on
P9754), according to the following criteria:

- Newly diagnosed, previously untreated biopsy-proven moderate or high grade
osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal
or periosteal sarcoma are ineligible

- < 31 years of age at time of initial osteosarcoma diagnosis

- Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of
therapy can extend beyond 2002

- No evidence of poor or low cardiac function at time of initial osteosarcoma
diagnosis; if reports from the time are available: shortening fraction >= 28% by
echocardiogram and within the institutional normative range for age, or
radionuclide angiogram ejection fraction >= 50%; if imaging reports from the time
are no longer available, there must be no documentation within available medical
records that suggest poor or low cardiac function at time of diagnosis

- Comparison subject must have institutional records (e.g., clinic note, treatment
summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m^2
of doxorubicin (doses within 10% are acceptable); this includes initial therapy
as well as any subsequent therapy for relapse or second cancer, if relevant; as
such, comparison subjects who have had osteosarcoma relapse or subsequent
malignancies remain eligible so long as they meet all other eligibility criteria

- No anthracycline or anthraquinone aside from doxorubicin was ever given as part
of initial or subsequent therapies

- No exposure to DRZ at any point in time

- All patients and/or their parents or legal guardians must sign a written informed
consent

- STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3

- Individuals diagnosed with cancer prior to age 21 years, who required treatment with
chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after
completing anti-cancer-therapy for at least 1 year

- Must have screening echocardiograms for heart function as part of cancer therapy and
off-therapy evaluations available (Digital Imaging and Communications in Medicine
[DICOM] format). Images from Video Home System (VHS) tapes and reports only (without
images) are not suitable

- Cannot have a known history of congenital heart disease (patent foramen ovale remain
eligible) or underlying genetic syndrome associated with abnormal cardiovascular
development or health (e.g., down syndrome)

- Based on echocardiography, must have either left ventricular fractional shortening =<
28.0% or ejection fraction =< 50.0% on at least two occasions, with at least one of
these measurements occurring after cancer therapy completion and be in the absence of
sepsis or any uncontrolled infection

- If the fractional shortening or ejection fraction criteria is only met on one
occasion, this must be after cancer therapy completion, be in the absence of sepsis or
any uncontrolled infection, and the patient must have subsequently started on chronic
medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme
[ACE]-inhibitor, angiotensin receptor blocker) lasting at least 6 months

- For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug
Administration (FDA), and National Cancer Institute (NCI) requirements for human
studies must be met
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [2] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maine
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Mississippi
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Nevada
Country [18] 0 0
United States of America
State/province [18] 0 0
New Hampshire
Country [19] 0 0
United States of America
State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New Mexico
Country [21] 0 0
United States of America
State/province [21] 0 0
New York
Country [22] 0 0
United States of America
State/province [22] 0 0
North Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Ohio
Country [24] 0 0
United States of America
State/province [24] 0 0
Oklahoma
Country [25] 0 0
United States of America
State/province [25] 0 0
Oregon
Country [26] 0 0
United States of America
State/province [26] 0 0
Pennsylvania
Country [27] 0 0
United States of America
State/province [27] 0 0
Rhode Island
Country [28] 0 0
United States of America
State/province [28] 0 0
South Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Texas
Country [30] 0 0
United States of America
State/province [30] 0 0
Vermont
Country [31] 0 0
United States of America
State/province [31] 0 0
Virginia
Country [32] 0 0
United States of America
State/province [32] 0 0
Washington
Country [33] 0 0
United States of America
State/province [33] 0 0
Wisconsin
Country [34] 0 0
Canada
State/province [34] 0 0
Alberta
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
Puerto Rico
State/province [37] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This clinical trial studies the effects of dexrazoxane hydrochloride on biomarkers associated
with cardiomyopathy and heart failure after cancer treatment. Studying samples of blood in
the laboratory from patients receiving dexrazoxane hydrochloride may help doctors learn more
about the effects of dexrazoxane hydrochloride on cells. It may also help doctors understand
how well patients respond to treatment.
Trial website
https://clinicaltrials.gov/show/NCT01790152
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric J Chow
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01790152