Clinical trial NCT02677714: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Doxorubicin Induced Cardiomyopathy
Lead sponsor: Advanced Accelerator Applications
Sponsor class: INDUSTRY
First posted: 2016-02-09
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility
timeFrame: Day 0 (Baseline)
Secondary outcomes:
measure: 99mTc-rhAnnexin V-128 Myocardial Uptake
timeFrame: 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)
measure: Changes in Left Ventricular (LV) Function
timeFrame: 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)
measure: Changes in the Cardiotoxicity Biomarkers (Troponin and NT-proBNP)
timeFrame: 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)
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: