Markers of Anthracycline-Related Cardiac Muscle Injury

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01112800
First received: April 26, 2010
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

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.


Condition
Osteosarcoma
Ewing's Sarcoma Family of Tumors
Rhabdomyosarcoma
Non-rhabdomyosarcoma Soft Tissue Sarcomas

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Markers of Anthracycline-Related Cardiac Muscle Injury

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Imaging measurement of potential cardiac muscle injury markers before and after cumulative anthracycline exposure. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    This study will serially evaluate imaging tests in previously untreated patients with osteosarcoma, Ewing's sarcoma family of tumors, 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.


Biospecimen Retention:   Samples Without DNA

A blood sample will be collected at baseline, prior to and at the end of each doxorubicin infusion (48- or 72-hour) and following completion of chemotherapy for osteosarcoma, ESFT, rhabdomyosarcoma or intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas.cTn-T and NT-BNP will be measured at baseline, prior to and at the end of each doxorubicin infusion (48- or 72-hour) and following completion of chemotherapy for osteosarcoma, ESFT, rhabdomyosarcoma or intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas.


Enrollment: 0
Study Start Date: May 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Participants
Previously untreated patients referred to St. Jude Children's Research Hospital (SJCRH) between the ages of 0 and 21 years with a diagnosis of osteosarcoma, ESFT, rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes administration of a cumulative anthracycline dose ≥ 375 mg/m2.

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Previously untreated patients referred to St. Jude Children's Research Hospital (SJCRH) between the ages of 0 and 21 years with a diagnosis of osteosarcoma, ESFT, rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes administration of a cumulative anthracycline dose ≥ 375 mg/m2.

Criteria

Inclusion Criteria:

  • Between 0 and 21 years of age
  • Diagnosis of osteosarcoma, Ewing Sarcoma Family of Tumors, rhabdomyosarcoma, or intermediate or high-risk non-rhabdomyosarcoma soft tissue sarcoma
  • Planned treatment includes administration of a cumulative anthracycline dose ≥ 375 mg/m2

Exclusion Criteria:

  • Pregnant Females
  • Patients with a history of cancer prior to the current malignancy
  • Patients whose treatment will include radiation therapy to a volume that will include the heart
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01112800

Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Daniel Green, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01112800     History of Changes
Other Study ID Numbers: MARCI
Study First Received: April 26, 2010
Last Updated: June 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Anthracycline
Cardiac Muscle Injury
Doxorubicin
Doppler Imaging
Intermediate non-rhabdomyosarcoma soft tissue sarcomas
High-risk non-rhabdomyosarcoma soft tissue sarcomas

Additional relevant MeSH terms:
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Ewing's
Sarcoma
Wounds and Injuries
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Myosarcoma
Neoplasms, Muscle Tissue

ClinicalTrials.gov processed this record on April 23, 2014