99mTc-ADAPT6 SPECT-based Non-invasive Quantification of HER2-expression in Breast Cancer With Metastatic Lymph Nodes

Study Overview
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Brief Summary
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An open-label, single center study with 99mTc-ADAPT6 SPECT and biopsies of primary tumour and metastatic lymph nodes in breast cancer patients, where the primary endpoint of the study is to find out the correlation between the HER2 expression measured by 99mTc-ADAPT6 SPECT and standard histopathology from relevant tumor and lymph node biopsies.

Detailed Description
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Overall goal of the project: To determine HER2 expression level in primary breast cancer and axillary lymph node metastases before neoadjuvant targeted (trastuzumab or trastuzumab+pertuzumab) therapy.

Official Title
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SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Primary Tumour and Metastatic Axillary Lymph Nodes Using Technetium-99m-labelled ADAPT6 Molecule-based 99mTc-ADAPT6.

Conditions
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Breast Cancer, Female

Intervention / Treatment
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* Drug: ADAPT6-SPECT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is > 18 years of age Diagnosis of primary breast cancer with lymph node metastases Availability of results from HER2 status previously determined on material from the primary tumor and metastatic LN, either a. HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or b. HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative Hematological, liver and renal function test results within the following limits: White blood cell count: > 2.0 x 109/L Hemoglobin: > 80 g/L Platelets: > 50.0 x 109/L ALT, ALP, AST: =< 5.0 times Upper Limit of Normal Bilirubin =< 2.0 times Upper Limit of Normal Serum creatinine: Within Normal Limits A negative pregnancy test for all patients of childbearing potential. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception for at least 30 days after study termination 7. Subject is capable to undergo the diagnostic investigations to be performed in the study 8. Informed consent Exclusion Criteria: Any system therapy (chemo-/targeted therapy) Second, non-breast malignancy Active current autoimmune disease or history of autoimmune disease Active infection or history of severe infection within the previous 3 months (if clinically relevant at screening) 4. Known HIV positive or chronically active hepatitis B or C Administration of other investigational medicinal product within 30 days of screening Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Diagnostic Test: ADAPT6-SPECT Diagnostic SPECT for HER2 expression in primary tumour and metastatic lymph nodes
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2-positive patients<br>Maximum 15 evaluable subjects with HER2-positive status in primary tumour before chemo/targeted therapy have to be enrolled in the study. Subjects withdrawn from the study for any reason will be replaced. | Drug: ADAPT6-SPECT<br>* Diagnostic SPECT for HER2 expression in primary tumour and metastatic lymph nodes<br>* Other names: Diagnostic ADAPT6-SPECT injection;|
| Experimental: HER2-negative patients<br>Maximum 15 evaluable subjects with HER2-negative status in primary tumour before chemo/targeted therapy have to be enrolled in the study. Subjects withdrawn from the study for any reason will be replaced. | Drug: ADAPT6-SPECT<br>* Diagnostic SPECT for HER2 expression in primary tumour and metastatic lymph nodes<br>* Other names: Diagnostic ADAPT6-SPECT injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPECT/CT-based 99mTc-ADAPT6 uptake value in tumor lesions (SUV) | SPECT/CT-based 99mTc-ADAPT6 uptake value in tumor lesions measured as 99mTc-ADAPT6 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 hours after injection and measured in SUV | 2 hours | 
| SPECT/CT-based 99mTc-ADAPT6 uptake value in metastatic lymph nodes (SUV) | SPECT/CT-based 99mTc-ADAPT6 uptake value in metastatic lymph nodes SUV measured as 99mTc-ADAPT6 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 hours after injection and measured in SUV | 2 hours | 
| Tumor-to-background ratio (SPECT) | The SPECT-based tumor-to-background ratio will be calculated as follows: the value of 99mTc-ADAPT6 uptake coinciding with tumor lesions (SUV) will be divided by the value of 99mTc-ADAPT6 uptake coinciding with the regions without pathological findings (SUV) | 2 hours | 
| LN-to-background LN ratio (SPECT) | The SPECT-based LN-to-background LN ratio will be calculated as follows: the value of 99mTc-ADAPT6 uptake coinciding with LN lesions (SUV) will be divided by the value of 99mTc-ADAPT6 uptake coinciding with the regions without pathological findings (SUV) | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matching test rate (percentage) | Comparison of the 99mTc-ADAPT6 accumulation in the primary tumor and metastatic lymph nodes with the results of morphological and immunohistochemical studies. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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99mTc-ADAPT6, Breast Cancer, metastatic lymph nodes, HER2 expression