Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment

Sponsor
Children's Oncology Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT01790152
Collaborator
National Cancer Institute (NCI) (NIH)
420
79
112.9
5.3
0

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Assessment of Therapy Complications
  • Other: Laboratory Biomarker Analysis
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine whether leukemia and lymphoma patients from P9404, P9425, P9426, and Dana Farber Cancer Institute (DFCI) 95-01 randomized to the experimental dexrazoxane hydrochloride (DRZ) arms have decreased markers of cardiomyopathy/heart failure (CHF) compared with patients on the standard arm.

  2. To determine whether osteosarcoma patients from P9754 (all received DRZ) have decreased markers of cardiomyopathy/heart failure (CHF) compared with similarly treated osteosarcoma patients diagnosed during the same time period, but who did not receive DRZ.

  3. To evaluate whether the cardioprotective effect of DRZ is modified by anthracycline (anthracycline analogue GPX-150) dose, chest radiation, and demographic factors (age at cancer diagnosis, current age, sex).

SECONDARY OBJECTIVES:
  1. To determine whether leukemia and lymphoma patients from P9404, P9425, P9426, and DFCI 95-01 on the DRZ arms experienced differential rates of overall-survival and event-free survival compared with the standard therapy arms.

  2. To determine whether projected quality-adjusted life years (QALY) differed by DRZ status, accounting for premature cardiac disease, primary disease relapse, and second cancers.

  3. Determine the longitudinal trajectory of 2-dimensional echocardiographic parameters (focusing on left ventricular [LV] function and remodeling/geometric changes that can be reliably re-measured) among patients from time of cancer treatment through subsequent follow-up.

OUTLINE:

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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
420 participants
Observational Model:
Case-Only
Time Perspective:
Prospective
Official Title:
Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy
Actual Study Start Date :
Aug 5, 2013
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
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: Assessment of Therapy Complications
Ancillary studies

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. Left ventricular function and measures of pathologic remodeling (i.e., thickness-to-dimension ratio) assessed using standard 2-dimensional, M-mode, and Doppler echocardiogram [Baseline]

      Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.

    2. Differences in serum biomarkers (particularly cardiac troponins and natriuretic peptides) [Baseline]

      Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.

    Secondary Outcome Measures

    1. Quality of life based on self-report instruments [Baseline]

      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.

    2. Primary disease relapse [Baseline]

      An analytic Markov model will be created and used.

    3. Second cancer rates [Baseline]

      An analytic Markov model will be created and used.

    4. Longitudinal trajectory of 2-dimensional echocardiographic parameters [From time of cancer treatment to subsequent follow-up]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    3 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    4 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    5 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    6 Valley Children's Hospital Madera California United States 93636
    7 Kaiser Permanente-Oakland Oakland California United States 94611
    8 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    9 Rady Children's Hospital - San Diego San Diego California United States 92123
    10 Yale University New Haven Connecticut United States 06520
    11 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
    12 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    13 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    14 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
    15 Nemours Children's Hospital Orlando Florida United States 32827
    16 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    17 Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida United States 33607
    18 Saint Mary's Hospital West Palm Beach Florida United States 33407
    19 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    20 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    21 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    22 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    23 University of Illinois Chicago Illinois United States 60612
    24 Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois United States 60453
    25 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
    26 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    27 Maine Children's Cancer Program Scarborough Maine United States 04074
    28 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    29 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    30 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    31 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    32 Ascension Saint John Hospital Detroit Michigan United States 48236
    33 Hurley Medical Center Flint Michigan United States 48503
    34 University of Mississippi Medical Center Jackson Mississippi United States 39216
    35 Columbia Regional Columbia Missouri United States 65201
    36 Washington University School of Medicine Saint Louis Missouri United States 63110
    37 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    38 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109
    39 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
    40 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
    41 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    42 Hackensack University Medical Center Hackensack New Jersey United States 07601
    43 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    44 Roswell Park Cancer Institute Buffalo New York United States 14263
    45 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
    46 University of Rochester Rochester New York United States 14642
    47 Stony Brook University Medical Center Stony Brook New York United States 11794
    48 State University of New York Upstate Medical University Syracuse New York United States 13210
    49 Mission Hospital Asheville North Carolina United States 28801
    50 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    51 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    52 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    53 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    54 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    55 Oregon Health and Science University Portland Oregon United States 97239
    56 Saint Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
    57 Rhode Island Hospital Providence Rhode Island United States 02903
    58 Medical University of South Carolina Charleston South Carolina United States 29425
    59 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    60 Medical City Dallas Hospital Dallas Texas United States 75230
    61 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    62 Cook Children's Medical Center Fort Worth Texas United States 76104
    63 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    64 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    65 University of Vermont and State Agricultural College Burlington Vermont United States 05405
    66 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    67 Seattle Children's Hospital Seattle Washington United States 98105
    68 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
    69 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    70 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    71 Perth Children's Hospital Perth Western Australia Australia 6009
    72 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    73 McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario Canada L8N 3Z5
    74 Children's Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1
    75 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    76 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    77 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5
    78 Centre Hospitalier Universitaire de Quebec Quebec Canada G1V 4G2
    79 San Jorge Children's Hospital San Juan Puerto Rico 00912

    Sponsors and Collaborators

    • Children's Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Eric J Chow, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT01790152
    Other Study ID Numbers:
    • ALTE11C2
    • NCI-2012-03196
    • S0004187
    • ALTE11C2
    • COG-ALTE11C2
    • ALTE11C2
    • R01CA211996
    • U10CA095861
    • UG1CA189955
    First Posted:
    Feb 13, 2013
    Last Update Posted:
    Mar 22, 2022
    Last Verified:
    Jul 1, 2021

    Study Results

    No Results Posted as of Mar 22, 2022