Markers of Anthracycline-Related Cardiac Muscle Injury
Summary
Anthracycline antibiotics are included in the chemotherapy regimens of approximately 82% of patients with bone cancer and 44% of those with soft tissue sarcoma diagnosed in childhood or adolescence. Impaired cardiac function occurs after treatment with anthracyclines. The frequency of impairment increases with increasing cumulative dose. There are inadequate data regarding the relationship between doxorubicin administration and changes in serum levels of cardiac troponin T (cTn-T) or I (cTn-I), N-terminal (NT) brain natriuretic peptide (BNP), or tissue Doppler imaging parameters.
This non-therapeutic study proposes a prospective, single arm study of serial changes in tissue Doppler imaging parameters, cTn-T and NT-BNP in children and adolescents with malignant bone and soft tissue tumors whose planned chemotherapy includes treatment with ≥ 375 mg/m2 of doxorubicin.
The proposed study will rigorously evaluate the usefulness of serial determinations of tissue Doppler imaging, cTn-T and NT-BNP for very early identification of anthracycline-related myocardial injury. Demonstration that one or more of these markers identifies subclinical myocardial damage and that biomarker or tissue Doppler imaging parameters exhibit a dose-response relationship with cumulative doxorubicin dose would facilitate intervention trials in patients at risk for anthracycline cardiomyopathy.
Description
The primary aim of this proposal is to serially evaluate imaging tests in previously untreated patients with osteosarcoma, Ewing's Sarcoma Family of Tumors(ESFT), rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes a cumulative doxorubicin dose ≥ 375 mg/m2 to determine if serial levels of one or more of these potential markers of cardiac muscle injury obtained prior to each infusion of doxorubicin and at the completion of chemotherapy correlate with increasing cumulative anthracycline exposure.
The secondary aim of the study is to estimate the proportion of patients with decreased (evaluation j - evaluation j+1) peak longitudinal systolic strain (ε) or strain rate (SR), peak radial systolic ε or SR, peak radial systolic myocardial velocity or peak longitudinal systolic myocardial velocity among those who have a shortening fraction (SF) ≥ 29% prior to each infusion of anthracycline. This study will evaluate whether the serum levels of cTn-T and/or NT-BNP will increase following doxorubicin administration. The study will evaluate whether the serum levels of cTn-T and/or NT-BNP will increase with increasing cumulative doxorubicin dose.
Study Design
Observational Model: Cohort, Time Perspective: Prospective
Conditions
Osteosarcoma
Location
St . Jude Children's Research Hospital
Memphis
Tennessee
United States
38105
Status
Recruiting
Source
St. Jude Children's Research Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01112800
- Information obtained from ClinicalTrials.gov on January 03, 2013
Medical and Biotech [MESH] Definitions
Tumor Suppressor Protein P53
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Li-fraumeni Syndrome
Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.
Clinical Trials
None
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