HER2 Expression Detection in Breast Cancer Using 99mTc-NM-02

Study Overview
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Brief Summary
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A 99mTc-labeled anti-HER2-sdAb (99mTc-NM-02) will be developed for SPECT/CT assessment of HER2 expression in breast cancer patients. Its safety, radiation dosimetry and biodistribution, and the relationship between tumor uptake and HER2 immunohistochemistry results will be investigated.

Detailed Description
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To evaluate the safety, dosimetry and efficacy of 99m-Tc labeled anti-HER2 single domain antibody (sdAb) (Product Code Name: 99mTc-NM-02) SPECT/ CT imaging of HER2 expression in Breast Cancer and compare it with the existing gold standard  HER2 expression detection by biopsy tissue immunohistochemistry (IHC) and/or Fluorescence In Situ Hybridization (FISH) method. It is also to establish a new clinical method of non-invasive HER2 expression detection in breast cancer using 99m-Tc labeled anti-HER2 sdAb

Official Title
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Technetium-99m Labeled Anti-HER2 sdAb (99m-Tc-NM-02) for HER2 Expression Detection in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Injection of 99mTc-NM-02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult female, age 18 years or older Prior diagnosis of breast cancer Willing to participate in this study and given written informed consent AST, ALT, BUN, Cr not more than double the normal values Subjects of childbearing potential must be willing to undergo a pregnancy test prior to enrolment Exclusion Criteria: Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period) Breastfeeding (subjects in lactation) No biopsy tissue sample can be provided for HER2 expression detection Subjects with pacemakers Hepatitis B virus infection (including carriers) at screening, ie hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (anti-HCV) positive, or acquired immunodeficiency disease (HIV) infected, or serum syphilis positive person Abnormal liver function during baseline screening period : AST or ALT> 2 times the upper limit of normal value (ULN), if the marginal increase of a single index is judged as having no clinical significance by the investigator, it can be retested during the screening period. Once, if ≤ 2 times ULN after retesting, consider enrolling). Impaired renal function during screening: serum creatinine or urea nitrogen > 1.5 times ULN. Within 4 months prior to the baseline screening period , myocardial infarction or other cardiac events requiring hospitalization (unstable angina, etc.), cerebrovascular accident, transient ischemic attack, acute congestive Heart failure or severe arrhythmia (ventricular arrhythmia, atrioventricular block above II) Subjects with pulmonary embolism or deep vein thrombosis Various infections that the investigators consider unsuitable for study, including but not limited to patients with various infections requiring further treatment, such as urinary tract infections, respiratory infections, and diabetic foot infections. Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Injection of 99mTc-NM-02<br>All breast cancer patients recruited to the study will be administered 3-12 MBq/kg of 99m-Tc-NM-02 (99m-Tc labeled anti-HER2 sdAb) in a single dose injection | Drug: Injection of 99mTc-NM-02<br>* Patient will be injected with microdose (<100ug) of 99mTc-NM-02 radiotracer<br>* Other names: anti-HER2 SPECT/CT radiotracer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan | Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99m-Tc-NM-02 in breast malignant lesions. A 4 point system will be used to interpret the scans for abnormalities. It is categorised as such: score 0, no abnormal increased uptake; score 1, low increased uptake; score 2, moderate increased uptake; score 3, high increased uptake. The lesion will be considered positive for malignancy if the score is 2 or higher. | 1 year | 
| Semiquantitative Assessment of Breast and other Metastatic Lesions in 99mTc-NM-02 SPECT/CT Scan | Each subject will be administered 3-12 MBq/kg of 99mTc-NM-02 and the semiquantitative analysis of the region of interest (ROI) will be performed in breast and other metastatic lesions. Higher level of HER2 expression (Tumor proportion score, TPS), higher ROI in tumor. | 1 year | 
| Safety of 99mTc-NM02 through Adverse Event Monitoring | Subjects will be observed for safety after administration of 99mTc-NM-02, and will do follow up at 48h p.i. Subjects will do blood test to observe for abnormalities in clinical parameters and compare to baseline results. | 2 days | 
| Safety of 99m-Tc-NM-02 through Adverse Event Monitoring | Subjects will be observed for safety after administration of 99mTc-NM-02, and will do follow up at 7d p.i. Subjects will be contacted by investigator by phone and asked several questions related to subject's health after 99m-Tc-NM-02 injection and concomitant drugs. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HER2 Expression Heterogeneity | Biopsy tissue sample IHC and FISH HER2 test results from subject's primary tumor will indicate its HER2 expression level, this results will be compared with our radiotracer uptake in the primary tumor and will look for heterogeneity while observing for uptake in other metastatic lesions. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2, single domain antibody (sdAb), SPECT/CT imaging