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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy

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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine whether patients randomized to the experimental dexrazoxane hydrochloride (DRZ) arms have decreased markers of cardiomyopathy/heart failure (CHF) compared with patients on the standard arm.

II. 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:

I. To determine whether patients on the DRZ arms experienced differential rates of overall-survival and event-free survival compared with the standard therapy arms.

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

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.


Sponsor: Children's Oncology Group

Current Primary Outcome:

  • Left ventricular thickness-to-dimension ratio assessed using standard 2-dimensional. [ Time Frame: 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.
  • Left ventricular thickness-to-dimension ratio assessed using M-mode. [ Time Frame: 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.
  • Left ventricular thickness-to-dimension ratio assessed using Doppler echocardiogram. [ Time Frame: 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.


Original Primary Outcome: Left ventricular (LV) thickness-to-dimension ratio [ Time Frame: 2 years ]

A decrease in echocardiographically derived measure of pathologic left ventricle (LV) remodeling which has been shown to be an important earlier surrogate measure of subsequent heart failure in both anthracycline-exposed pediatric cancer survivors5 and in the general pediatric and adult cardiomyopathy/heart failure population. This ratio can be derived from standard measurements.


Current Secondary Outcome:

  • Differences in serum biomarkers (particularly cardiac troponins and natriuretic peptides) [ Time Frame: Baseline ]
  • Primary disease relapse [ Time Frame: Baseline ]
    An analytic Markov model will be created and used.
  • Quality of life based on self-report instruments [ Time Frame: Baseline ]
    An analytic Markov model will be created and used. Estimates and their 95% confidence will be included to explore the sensitivity of any QALY estimates.
  • Second cancer rates [ Time Frame: Baseline ]
    An analytic Markov model will be created and used.


Original Secondary Outcome:

  • Differences in serum biomarkers [ Time Frame: 2 years ]
    Particularly cardiac troponins and natriuretic peptides associated with acute changes following anthracycline exposure will be examined. Analyses involving markers of inflammation (hs-CRP, TNF, IL6) and more novel markers associated with heart failure in the general population (galectin-3, ST2, growth differentiation factor-15) are exploratory.
  • Quality of life [ Time Frame: 2 years ]
    Based on self-report instruments will be factored into QALY estimates to answer the secondary aims.
  • Update primary disease relapse and second cancer rates [ Time Frame: 2 years ]
    Given additional elapsed time since last follow-up used in the prior published analyses,11-13 primary disease relapse and second cancer rates will be updated.


Information By: Children's Oncology Group

Dates:
Date Received: February 11, 2013
Date Started: August 2013
Date Completion:
Last Updated: October 24, 2016
Last Verified: October 2016