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

NCT02677714 | Terminated Phase 2 Results DMC

• 2 other identifiers: AAA-Annexin-05CAAA113A42202
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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. 1.Screening/baseline, i.e. 2 weeks prior to initiating AC treatment (Visit 1)
2. 2.After the 2nd and before the 3rd cycle of AC treatment (Visit 2)
3. 3.After the 4th cycle of AC treatment and within 2 weeks (Visit 3)
4. 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.

Conditions

Breast Cancer; Doxorubicin Induced Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 0 (Baseline)

Secondary Outcomes (3)

• 99mTc-rhAnnexin V-128 Myocardial Uptake

  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)

• Changes in Left Ventricular (LV) Function

  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)

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

  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)

Study Arms (1)

Patients with breast cancer receiving chemotherapy

EXPERIMENTAL

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.

Radiation: 99mTc-rhAnnexin V-128

Interventions

99mTc-rhAnnexin V-128 RADIATION

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

Patients with breast cancer receiving chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Unwillingness to provide consent

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Due to the early termination of the trial and the fact that only 2 patients were enrolled in the Phase II of the study, the efficacy endpoints of the trial were not addressed (summary statistics were not performed).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: February 9, 2016
• Study Start: November 2, 2016
• Primary Completion: October 12, 2018
• Study Completion: October 12, 2018
• Last Updated: December 11, 2020
• Results First Posted: December 11, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)