Overview

This trial is active, not recruiting.

Conditions breast cancer, doxorubicin induced cardiomyopathy
Treatment 99mtc-rhannexin v-128
Phase phase 2
Sponsor Advanced Accelerator Applications
Start date April 2016
End date December 2016
Trial size 30 participants
Trial identifier NCT02677714, AAA-Annexin-05

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Experimental)
Patients with early stage breast cancer receiving 4 cycles of doxorubicin-based chemotherapy (doxorubicin:60 mg/m² and cyclophosphamide: 600 mg/m²) at about 2 week intervals followed by paclitaxel. Patients will undergo 99mTc-rhAnnexin V-128 scans at 60 min and 2 hrs and a Cardiac Magnetic Resonance Imaging at baseline, after the 2nd cycle of chemotherapy, after the 4th cycle of chemotherapy and 12 weeks after the last cycle of chemotherapy.
99mtc-rhannexin v-128

Primary Outcomes

Measure
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)
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)

Secondary Outcomes

Measure
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)
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)
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)
Adverse events
time frame: From baseline up to 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks)
Laboratory assessment
time frame: Baseline and 12 weeks after the 4th cycle of doxorubicin (cylce intervals = about 2 weeks)

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: 1. Females ≥ 18 years of age with histologically confirmed early stage (Stage I, II or III) human epidermal growth factor receptor 2 negative breast cancer and planned for (neo)adjuvant doxorubicin-based chemotherapy (AC every 2 weeks x 4 cycles) 2. Eastern Cooperative Oncology Group Status (ECOG) ≤ 2 3. Able and willing to comply with the study procedures Exclusion Criteria: 1. Pregnancy or lactation 2. Baseline LVEF < 54% as determined by echocardiography (within 2 months prior to enrollment) 3. Moderate or severe valvular stenosis or regurgitation 4. History of atrial fibrillation or flutter 5. History of any disease or relevant physical or psychiatric condition which may interfere with the study objectives at the investigator judgment 6. Know hypersensitivity to the investigational product or any of its components 7. Prosthetic valve or pacemaker 8. Claustrophobia or inability to lie still in a supine position 9. Contraindication(s) to the CMRI procedure 10. Participation in another clinical trial within 4 weeks before study inclusion, except for patients who have participated or who are currently participating in a study without any study drug administration 11. Unwillingness to provide consent

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Advanced Accelerator Applications.