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

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

99mTc-rhAnnexin V-128

About this trial

This is an interventional diagnostic trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

Females >= 18 years of age with histologically confirmed early stage (Stage I, II or III) HER-2 negative breast cancer and planned for (neo)adjuvant doxorubicin-based chemotherapy (AC every 2 or 3 weeks x 4 cycles)
Eastern Cooperative Oncology Group Status (ECOG) ≤ 2
Able and willing to comply with the study procedures

Exclusion criteria:

Pregnancy or lactation
Moderate or severe valvular stenosis or regurgitation
History of atrial fibrillation or flutter
History of any disease or relevant physical or psychiatric condition which may interfere with the study objectives at the investigator judgment
Know hypersensitivity to the investigational product (IP) or any of its components
Prosthetic valve or pacemaker
Claustrophobia or inability to lie still in a supine position
Contraindication(s) to the CMRI procedure
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
Unwillingness to provide consent

Sites / Locations

University of Ottawa Heart Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with breast cancer receiving chemotherapy

Arm Description

After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy.

Outcomes

Primary Outcome Measures

Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility

The feasibility of imaging apoptotic activity using 99mTc-rhAnnexin V-128 was assessed in the first 10 patients who enrolled and completed the PoC phase of the study by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed.

Secondary Outcome Measures

99mTc-rhAnnexin V-128 Myocardial Uptake

Single-Photon Emission Computed Tomography (SPECT)/Computed Tomography (CT) scans of the thorax were acquired with a dual head SPECT/CT gamma camera with low-energy high-resolution collimators at 1 and 2 hours post-injection at each collection time point and were to be compared to Baseline. Myocardial uptake was measured from regions of interest (ROIs) placed over the myocardium on the SPECT images coregistered with the corresponding CT images for anatomic delineation. Myocardial uptake was expressed either in absolute units (% injected dose/g) or as a standardized uptake value (SUV). Only descriptive analysis performed.

Changes in Left Ventricular (LV) Function

The worsening of LV function was to be assessed by comparing cardiac magnetic resonance imaging (CMRI) left ventricular ejection fraction (LVEF) after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline. Only descriptive analysis performed.

Changes in the Cardiotoxicity Biomarkers (Troponin and NT-proBNP)

The differences of LV function after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline were to be correlated with the changes in cardiotoxicity biomarkers: Troponin and N Terminal pro B-type Natriuretic Peptide (NT-proBNP). Only descriptive analysis performed.

Full Information

NCT ID

NCT02677714

First Posted

January 26, 2016

Last Updated

November 17, 2020

Sponsor

Advanced Accelerator Applications

1. Study Identification

Unique Protocol Identification Number

NCT02677714

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Terminated

Why Stopped

Sponsor Decision based on strategic considerations

Study Start Date

November 2, 2016 (Actual)

Primary Completion Date

October 12, 2018 (Actual)

Study Completion Date

October 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Advanced Accelerator Applications

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This was a single center, proof-of-concept (PoC), Phase II study. Patients with histologically confirmed early stage (Stage I, II or III) HER-2 negative breast cancer and scheduled to receive doxorubicin-based (neo)adjuvant therapy to be followed by paclitaxel or docetaxel as per clinical practice. The planned doxorubicin-based chemotherapy treatment consisted of doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 (AC) intravenous (IV) every 2 or 3 weeks for 4 cycles. Patients were scheduled for CMRI and 99mTc-rhAnnexin V-128 imaging (planar and SPECT / CT) at the following visits: Screening/baseline, i.e. 2 weeks prior to initiating AC treatment (Visit 1) After the 2nd and before the 3rd cycle of AC treatment (Visit 2) After the 4th cycle of AC treatment and within 2 weeks (Visit 3) At 12 weeks after the 4th cycle of AC treatment (Visit 4). The imaging procedures were conducted and analyzed. Bloodwork for cardiotoxicity biomarkers (troponin, N terminal pro B-type natriuretic peptide [NT-proBNP]) was performed at each visit.

Detailed Description

Overall, it was planned to recruit 30 adults with early stage breast cancer. The first 10 patients were to be enrolled in the PoC phase of the study to assess the potential of 99mTc-rhAnnexin V-128 in terms of imaging quality, uptake and medical relevance. Based on the results of the first 10 patients, the DMC was to decide whether to terminate the study or continue to the Phase II and enroll the next 20 planned patients. The maximum study duration was 26 (±4) weeks per patient (including the screening and follow-up periods). The sponsor decided to terminate the study earlier than planned due to strategic decisions to focus the AAA development portfolio on oncology theragnostics and not based on safety concerns.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Doxorubicin Induced Cardiomyopathy

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients with breast cancer receiving chemotherapy

Arm Type

Experimental

Arm Description

After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy.

Intervention Type

Radiation

Intervention Name(s)

99mTc-rhAnnexin V-128

Intervention Description

Kit for the preparation of 99mTc-rhAnnexin V-128

Primary Outcome Measure Information:

Title

Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility

Description

The feasibility of imaging apoptotic activity using 99mTc-rhAnnexin V-128 was assessed in the first 10 patients who enrolled and completed the PoC phase of the study by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed.

Time Frame

Day 0 (Baseline)

Secondary Outcome Measure Information:

Title

99mTc-rhAnnexin V-128 Myocardial Uptake

Description

Single-Photon Emission Computed Tomography (SPECT)/Computed Tomography (CT) scans of the thorax were acquired with a dual head SPECT/CT gamma camera with low-energy high-resolution collimators at 1 and 2 hours post-injection at each collection time point and were to be compared to Baseline. Myocardial uptake was measured from regions of interest (ROIs) placed over the myocardium on the SPECT images coregistered with the corresponding CT images for anatomic delineation. Myocardial uptake was expressed either in absolute units (% injected dose/g) or as a standardized uptake value (SUV). Only descriptive analysis performed.

Time Frame

60 and 120 minutes post injection at: Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin)

Title

Changes in Left Ventricular (LV) Function

Description

The worsening of LV function was to be assessed by comparing cardiac magnetic resonance imaging (CMRI) left ventricular ejection fraction (LVEF) after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline. Only descriptive analysis performed.

Time Frame

Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin)

Title

Changes in the Cardiotoxicity Biomarkers (Troponin and NT-proBNP)

Description

The differences of LV function after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline were to be correlated with the changes in cardiotoxicity biomarkers: Troponin and N Terminal pro B-type Natriuretic Peptide (NT-proBNP). Only descriptive analysis performed.

Time Frame

Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion criteria: Females >= 18 years of age with histologically confirmed early stage (Stage I, II or III) HER-2 negative breast cancer and planned for (neo)adjuvant doxorubicin-based chemotherapy (AC every 2 or 3 weeks x 4 cycles) Eastern Cooperative Oncology Group Status (ECOG) ≤ 2 Able and willing to comply with the study procedures Exclusion criteria: Pregnancy or lactation Moderate or severe valvular stenosis or regurgitation History of atrial fibrillation or flutter History of any disease or relevant physical or psychiatric condition which may interfere with the study objectives at the investigator judgment Know hypersensitivity to the investigational product (IP) or any of its components Prosthetic valve or pacemaker Claustrophobia or inability to lie still in a supine position Contraindication(s) to the CMRI procedure 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 Unwillingness to provide consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of Ottawa Heart Institute

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1Y 4W7

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

No

Breast Cancer, Doxorubicin Induced Cardiomyopathy

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial