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

NCT ID: NCT02677714

Last Updated: 2020-12-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-02
• Study Completion Date: 2018-10-12

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:

1. Screening/baseline, i.e. 2 weeks prior to initiating AC treatment (Visit 1)

2. After the 2nd and before the 3rd cycle of AC treatment (Visit 2)

3. After the 4th cycle of AC treatment and within 2 weeks (Visit 3)

4. 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.

Conditions

Breast Cancer; Doxorubicin Induced Cardiomyopathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Patients with breast cancer receiving chemotherapy

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.

Group Type: EXPERIMENTAL

99mTc-rhAnnexin V-128

Intervention Type: RADIATION

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

Interventions

99mTc-rhAnnexin V-128

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

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. 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)

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. Moderate or severe valvular stenosis or regurgitation

3. History of atrial fibrillation or flutter

4. History of any disease or relevant physical or psychiatric condition which may interfere with the study objectives at the investigator judgment

5. Know hypersensitivity to the investigational product (IP) or any of its components

6. Prosthetic valve or pacemaker

7. Claustrophobia or inability to lie still in a supine position

8. Contraindication(s) to the CMRI procedure

9. 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

10. Unwillingness to provide consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Advanced Accelerator Applications

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Countries

Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CAAA113A42202

Identifier Type: OTHER

Identifier Source: secondary_id

AAA-Annexin-05

Identifier Type: -

Identifier Source: org_study_id