Clinical Trial: 99mTc-rhAnnexin V-128 Imaging and Cardiotoxicity in Patients With Early Breast Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: 99mTc-rhAnnexin V-128 Imaging of Apoptosis and Cardiotoxicity in Relationship to Ventricular Function in Patients With Early Stage Breast Cancer Receiving Doxorubicin-Based Chemotherapy

Brief Summary:

The changes to the heart can be evaluated during the course of the chemotherapy with cardiac magnetic resonance imaging (CMRI) and left ventricular (LV) nuclear scans to look at left ventricular ejection fraction (LVEF). Serial LVEF evaluation can detect cardiotoxicity, usually after cardiac damage is present and most likely irreversible. Each patient's sensitivity to the chemotherapy is different.

The study is being done to assess the ability of the radiotracer 99mTc-rhAnnexin V-128 to image the cell damage from apoptosis, or cell death, in the heart from the effects of the chemotherapy. This may allow doctors to identify patients developing cardiotoxicity in the future. These patients may then benefit from changes in chemotherapy with dose alterations or changes to alternative drugs.

Detailed Summary:
Sponsor: Advanced Accelerator Applications

Current Primary Outcome:

• Imaging feasibility (Proof of Concept step) [ Time Frame: Change from baseline at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin (cylce intervals = about 2 weeks) ]
  Image quality, imaging agent uptake and clinical relevance of apoptosis imaging in the Evaluation of doxorubicin-induced cardiotoxicity will be determined by the Data Monitoring Committee (consensus on review of all patient all time point images vs their baseline image).
• Detection of doxorubicin-induced cardiotoxicity (Phase II step) [ Time Frame: Change from baseline at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin (cylce intervals = about 2 weeks) ]
  Overall ability of 99mTc-rhAnnexin V-128 to detect doxorubicin-induced cardiotoxicity will be based on the repeated analysis of uptake at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin vs baseline

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Timing and extent of 99mTc-rhAnnexin V-128 myocardial uptake [ Time Frame: Change from baseline at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin (cylce intervals = about 2 weeks) ]
  Timing and extent of 99mTc-rhAnnexin V-128 myocardial uptake will be determined by appropriate repeated measure analyses of uptake value in the areas of interest at each follow-up visit compared to baseline.
• CMRI LVEF [ Time Frame: Baseline and at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin and at 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks) ]
  The Left Ventricular function will be assessed by comparing Cardiac Magnetic Resonance Imaging (CMRI) Left Ventricular Ejection Fraction (LVEF) at each follow-up visit compared to baseline
• 99mTc-rhAnnexin V-128 myocardial uptake correlations [ Time Frame: Baseline and at 24hrs to 48hrs after the 2nd and the 4th cycles of doxorubicin and at 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks) ]
  99mTc-rhAnnexin V-128 uptake changes will be correlated with the changes in LVEF and cardiotoxicity biomarkers.
• Adverse events [ Time Frame: From baseline up to 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks) ]
  Type and incidence of AEs, as well as severity and relatedness to the study medication will be described
• Laboratory assessment [ Time Frame: Baseline and 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks) ]
  Type and incidence of abnormal Laboratory values will be analyzed by means of descriptive statistics with respect to the normal ranges of values provided by the laboratory

Original Secondary Outcome: Same as current

Information By: Advanced Accelerator Applications

Dates:
Date Received: January 26, 2016
Date Started: April 2016
Date Completion: April 2018
Last Updated: January 23, 2017
Last Verified: January 2017