NCT02677714

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

Terminated Phase 2 Results posted Last updated 11 December 2020

What this trial tests

Phase 2 trial testing 99mTc-rhAnnexin V-128 in Breast Cancer in 14 participants. Terminated before completion.

Timeline

2 November 2016

Primary endpoint
12 October 2018

12 October 2018

Quick facts

Lead sponsor	Advanced Accelerator Applications
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	14
Start date	2 November 2016
Primary completion	12 October 2018
Estimated completion	12 October 2018
Sites	1 location across Canada

Drugs / interventions tested

• 99mTc-rhAnnexin V-128 — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• Doxorubicin Induced Cardiomyopathy — all drugs for Doxorubicin Induced Cardiomyopathy →

Sponsor

Advanced Accelerator Applications — full company profile →

Who can join

18 and older, female only, with Breast Cancer or Doxorubicin Induced Cardiomyopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility Primary · Day 0 (Baseline)

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.

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	10

99mTc-rhAnnexin V-128 Myocardial Uptake Secondary · 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)

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 des

Day 0 - 60 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0035617	± 0.0051846
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0003306	± 0.0004675

Day 0 - 120 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0024177	± 0.0036831
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0002125	± 0.0003004

Visit 2 - 60 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0043825	± 0.0067130
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0008123	± 0.0011487

Visit 2 - 120 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0029255	± 0.0045063
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0004827	± 0.0006826

Visit 3 - 60 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0018097	± 0.0011105
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0000512	± 0.0000723

Visit 3 - 120 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0016232	± 0.0008994
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0002995	± 0.0004236

Visit 4 - 60 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0020756	± 0.0008986
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0010116	± 0.0014306

Visit 4 - 120 mins after injection

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.0018475	± 0.0005084
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.0006692	± 0.0009463

Changes in Left Ventricular (LV) Function Secondary · 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)

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.

Day 0

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	66.8	± 5.37
99mTc-rhAnnexin V-128 (Part II / Phase II)	64.0	± 2.83

Visit 2

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	66.3	± 6.07
99mTc-rhAnnexin V-128 (Part II / Phase II)	60.5	± 0.71

Visit 3

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	64.0	± 4.57
99mTc-rhAnnexin V-128 (Part II / Phase II)	65.0	± 1.41

Visit 4

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	63.6	± 4.22
99mTc-rhAnnexin V-128 (Part II / Phase II)	62.5	± 2.12

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

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.

Troponin - Day 0

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.015	± 0.001
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.015	± 0.000

Troponin - Visit 2

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.019	± 0.010
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.015	± 0.000

Troponin - Visit 3

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.025	± 0.019
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.015	± 0.000

Troponin - Visit 4

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	0.060	± 0.088
99mTc-rhAnnexin V-128 (Part II / Phase II)	0.028	± 0.018

NT-proBNP - Day 0

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	49.6	± 27.50
99mTc-rhAnnexin V-128 (Part II / Phase II)	60.0	± 63.64

NT-proBNP - Visit 2

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	271.8	± 399.76
99mTc-rhAnnexin V-128 (Part II / Phase II)	104.0	± 86.27

NT-proBNP - Visit 3

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	123.7	± 66.30
99mTc-rhAnnexin V-128 (Part II / Phase II)	85.0	± 49.50

NT-proBNP - Visit 4

Group	Value	95% CI
99mTc-rhAnnexin V-128 (Part I / Proof of Concept)	123.6	± 89.27
99mTc-rhAnnexin V-128 (Part II / Phase II)	74.0	± 29.70

Adverse events — posted to ClinicalTrials.gov

Time frame: From the signing of the informed consent until the last study-related procedure (up to 12 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

99mTc-rhAnnexin V-128 (Part I / Proof of Concept)

Serious: 1/12 (8%)

Deaths: 0/12

99mTc-rhAnnexin V-128 (Part II / Phase II)

Serious: 1/2 (50%)

Deaths: 0/2

Serious adverse events (9 terms)

Reaction	System	99mTc-rhAnnexin V-128 (Par…	99mTc-rhAnnexin V-128 (Par…
Anaemia	Blood and lymphatic system disorders	—	—
Pyrexia	Gastrointestinal disorders	—	—
Carbuncle	Infections and infestations	—	—
Cellulitis	Infections and infestations	—	—
Escherichia urinary tract infection	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Delirium	Psychiatric disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—

Other adverse events (33 terms — click to expand)

Reaction	System	99mTc-rhAnnexin V-128 (Par…	99mTc-rhAnnexin V-128 (Par…
Fatigue	General disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Neuropathy peripheral	Nervous system disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Palpitations	Cardiac disorders	—	—
Hypoacusis	Ear and labyrinth disorders	—	—
Vision blurred	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Duodenogastric reflux	Gastrointestinal disorders	—	—
Dysgeusia	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Oesophagitis	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Chest pain	General disorders	—	—
Febrile neutropenia	General disorders	—	—
Oral candidiasis	Infections and infestations	—	—
Respiratory tract infection	Infections and infestations	—	—
Fluid retention	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Insomnia	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Anxiety	Psychiatric disorders	—	—
Sleep disorder due to general medical condition, insomnia type	Psychiatric disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Herpes zoster	Skin and subcutaneous tissue disorders	—	—
Skin candida	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Anaemia, Pyrexia, Carbuncle, Cellulitis, Escherichia urinary tract infection, Urinary tract infection, Myalgia, Delirium.

Data from ClinicalTrials.gov NCT02677714 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. The Battlefield of Chemotherapy in Pediatric Cancers.
   Bo L, Wang Y, Li Y, Wurpel JND, et al · · 2023 · cited 24× · PMID 37046624 · DOI 10.3390/cancers15071963