99mTc-DARPinG3-based HER2 Expression Molecular Imaging in HER2-positive Breast Cancer During Chemo+Targeted Therapy

Study Overview
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Brief Summary
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An open-label, single center study with 99mTc-DARPinG3 SPECT and biopsies of primary tumour in HER2-positive Breast Cancer in dynamic of chemo+targeted therapy, where the primary endpoint of the study is to find out the correlation between the HER2 expression measured by 99mTc-DARPin G3 SPECT and standard histopathology from primary tumor in dynamic of chemo+targeted therapy.

Detailed Description
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none Methodology: Open-label, exploratory, single center study. The subjects will receive a single injection of the labelled tracer.

Official Title
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SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Using 99mTc-DARPinG3 in HER2-positive Breast Cancer Patients in Dynamic of Chemo+Targeted Therapy

Conditions
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Female, HER2-positive Breast Cancer

Intervention / Treatment
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* 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 tumour size ≥ 20 mm and with possible lymph node metastases; 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; In neoadjuvant all patients should receive standard chemo-targeted therapy according to the DCH+P (docetaxel + carboplatin+ trastuzumab+ pertuzumab) scheme; Injection of 99mTc-DARPinG3 at the dosage 3000 µg before and after 2 and 4 courses of chemo+targeted therapy in each HER2-positive breast cancer patient; Biopsies should be performed in all patients HER2-positive breast cancer patients before and after 2 and 4 courses of chemo+targeted therapy with evaluation of HER2 expression; 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: 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The tested injected doses of 99mTc-DARPinG3 3000 μg (SPECT)<br>Maximum (15) evaluable subjects with HER2-positive status in primary tumour before, after 2 and 4 courses of chemo+targeted therapy have to be enrolled in the study. Subjects withdrawn from the study for any reason will be replaced. | Drug: 99mTc-DARPinG3<br>* Diagnostic test (99mTc-DARPinG3-based SPECT) is used for the assessment of the effect of anticancer therapy.<br>* Other names: Diagnostic injection of 99mTc-DARPinG3.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPECT/CT-based 99mTc-DARPinG3 uptake value in primary tumor (standardized uptake value (SUV)) | SPECT/CT-based 99mTc-DARPinG3 uptake value in primary tumor lesions (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 before and after 2 and 4 courses of chemo+targeted therapy | 4 hours | 
| SPECT-based tumor-to-background ratio (conventional units) | The SPECT-based tumor-to-background ratio will be calculated as follows: the value of 99mTc-DARPinG3 uptake coinciding with primary tumor lesions (SUV) will be divided by the value of 99mTc-DARPinG3 uptake coinciding with the regions without pathological findings (SUV) before and after 2 and 4 courses of chemo+targeted therapy | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor-to-background ratio 99mTc-DARPinG3 SPECT versus immunohistochemical study | Comparison of the 99mTc-DARPinG3 accumulation (SUV or count-to-background ratio) in primary tumour with the results of morphological and immunohistochemical studies (score from 1 to 3) before and after 2 and 4 courses of chemo+targeted therapy | 4 hours | 

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