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

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ClinicalTrials.gov Identifier: NCT02677714
Recruitment Status : Recruiting
First Posted : February 9, 2016
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Advanced Accelerator Applications

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Doxorubicin Induced Cardiomyopathy Radiation: 99mTc-rhAnnexin V-128 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Study Start Date : April 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Patients with breast cancer receiving chemotherapy

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.

Radiation: 99mTc-rhAnnexin V-128



Primary Outcome Measures :
  1. 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).

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677714


Contacts
Contact: Terrence Ruddy, MD, FRCPC, FACC +1 613-761-4085 truddy@ottawaheart.ca

Locations
Canada, Ontario
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Terrence Ruddy, MD, FRCPC, FACC    +1 613-761-4085    TRuddy@ottawaheart.ca   
Contact: Marlie Poirier, Clinical Trial Coordinator       mpoirier@ottawaheart.ca   
Principal Investigator: Terrence Ruddy, MD, FRCPC, FACC         
Sub-Investigator: Kathryn Ascah, MD, FRCPC, FACC         
Sub-Investigator: Girish Dwivedi, PhD, MD         
Sub-Investigator: Glenn Wells, PhD         
Sub-Investigator: Olexiy Aseyev, MD         
Sub-Investigator: Susan Dent, MD         
Sub-Investigator: John Hilton, MD         
Sub-Investigator: Jeffrey Sulpher, MD         
Sponsors and Collaborators
Advanced Accelerator Applications

Responsible Party: Advanced Accelerator Applications
ClinicalTrials.gov Identifier: NCT02677714     History of Changes
Other Study ID Numbers: AAA-Annexin-05
First Posted: February 9, 2016    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Heart Diseases
Breast Neoplasms
Cardiomyopathies
Cardiotoxicity
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cardiovascular Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action