Molecular Imaging of HER2 Expression in HER2-positive Breast Cancer Using 99mTc-ADAPT6 vs 99mTc-DARPinG3

Study Overview
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Brief Summary
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An open-label, single center study with 99mTc-ADAPT6 and 99mTc-DARPinG3 SPECT and biopsies of primary tumour in HER2-positive Breast Cancer before system (chemo/targeted) therapy, where the primary endpoint of the study is to compare imaging properties of 99mTc-ADAPT6 and 99mTc-DARPin G3 SPECT in HER2-positive breast cancer patients.

Detailed Description
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The primary objectives are: Compare SPECT/CT imaging properties of 99mTc-ADAPT6 and 99mTc-DARPin G3 in HER2-positive primary tumour of breast cancer patients before system (chemo/targeted) therapy. The secondary objectives are: To compare the SPECT/CT tumor imaging data with the data concerning HER2 expression obtained by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) analysis of biopsy samples.

Official Title
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SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Using 99mTc-ADAPT6 and 99mTc-DARPinG3 in HER2-positive Breast Cancer Patients Before System (Chemo/Targeted) Therapy.

Conditions
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Breast Cancer Female

Intervention / Treatment
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* Drug: 99mTc-ADAPT6
* Drug: 99mTc-DARPinG3


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 possible lymph node metastases before system (chemo+targeted therapy); Availability of results from HER2 status previously determined on material from the primary tumor: HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive; Sequential injection of 99mTc-ADAPT6 and 99mTc-DARPinG3 in the interval of 3-4 days in each HER2-positive breast cancer patient; 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; Subject is capable to undergo the diagnostic investigations to be performed in the study; Informed consent Exclusion Criteria: 1. Second, non-breast malignancy 2. Active current autoimmune disease or history of autoimmune disease 3. 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 5. Administration of other investigational medicinal product within 30 days of screening 6. 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
Intervention Model: Single Group Assignment
Interventional Model Description: Diagnostic Test: ADAPT6-SPECT and DARPinG3-SPECT Diagnostic SPECT for HER2-positive Breast Cancer primary tumour
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2 positive breast cancer 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: 99mTc-ADAPT6<br>* One single injection of 99mTc-ADAPT6, followed by gamma camera imaging 2 hours after injection.<br>* Other names: SPECT;Drug: 99mTc-DARPinG3<br>* One single injection of 99mTc-DARPinG3, followed by gamma camera imaging 4 hours after injection.<br>* Other names: SPECT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 99mTc-ADAPT6 uptake (counts)/SUV | SPECT/CT-based 99mTc-ADAPT6 uptake value in primary tumor lesions (counts)/SUV of 99mTc-ADAPT6 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 hours after injection and measured in counts and SUV. | 2 hours | 
| 99mTc-ADAPT6 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 (counts/SUV) will be divided by the value of 99mTc-ADAPT6 uptake coinciding with the regions without pathological findings (counts) | 2 hours | 
| 99mTc-DARPinG3 uptake (counts)/SUV | SPECT/CT-based 99mTc-DARPinG3 uptake value in primary tumor lesions (counts)/SUV of 99mTc-DARPinG3 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 4 hours after injection and measured in counts and SUV | 4 hours | 
| 99mTc-DARPinG3 tumor-to-background ratio (SPECT) | The SPECT-based tumor-to-background ratio will be calculated as follows: the value of 99mTc-DARPinG3 uptake coinciding with tumor lesions (counts) will be divided by the value of 99mTc-DARPinG3 uptake coinciding with the regions without pathological findings (counts/the value of 99mTc-ADAPT6 and 99mTc-DARPinG3 uptake coinciding with tumor lesions (counts) will be divided by the value of 99mTc-ADAPT6 and 99mTc-DARPinG3 uptake coinciding with the regions without pathological findings (counts/SUV) | 4 hours | 
| 99mTc-ADAPT6 vs 99mTc-DARPinG3 uptake (counts)/SUV | Comparison of SPECT/CT-based 99mTc-ADAPT6 versus 99mTc-DARPinG3 uptake value in primary tumor lesions (counts)/SUV of 99mTc-ADAPT6 and 99mTc-DARPinG3 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 and 4 hours after injection and measured in counts and SUV. | 2 and 4 hours | 
| 99mTc-ADAPT6 vs 99mTc-DARPinG3 tumor-to-background ratio (SPECT) | Comparison of the value of 99mTc-ADAPT6 versus 99mTc-DARPinG3 uptake coinciding with tumor lesions (counts/SUV) divided by the value of 99mTc-ADAPT6 and 99mTc-DARPinG3 uptake coinciding with the regions without pathological findings (counts/SUV) | 2 and 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 99mTc-ADAPT6 vs immunohistochemical studies (percent) | Sensitivity (%) of the method is assessed by comparing the 99mTc-ADAPT6 accumulation in the primary tumor with the results of immunohistochemical studies | 2 hours | 
| 99mTc-DARPinG3 vs immunohistochemical studies (percent) | Sensitivity (%) of the method is assessed by comparing the 99mTc-DARPinG3 accumulation in the primary tumor with the results of immunohistochemical studies | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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99mTc-ADAPT6, 99mTc-DARPinG3, Breast Cancer, HER2 expression