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

Completed

• Conditions: Female; HER2-positive Breast Cancer
• Interventions: Drug: 99mTc-DARPinG3

• Registration Number: NCT05412459
• Lead Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences

Brief Summary

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

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

Study Timeline

• Study Start: 2022-05-01
• Status Verified: 2022-06
• Study First Submitted: 2022-06-02
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-09
• Primary Completion: 2022-12-31
• Study Completion: 2023-01-31
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

1. Subject is > 18 years of age;

2. Diagnosis of primary breast cancer with tumour size ≥ 20 mm and with possible lymph node metastases;

3. 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;

4. In neoadjuvant all patients should receive standard chemo-targeted therapy according to the DCH+P (docetaxel + carboplatin+ trastuzumab+ pertuzumab) scheme;

5. 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;

6. 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;

7. 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

8. 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;

9. Subject is capable to undergo the diagnostic investigations to be performed in the study;

10. 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
4. Administration of other investigational medicinal product within 30 days of screening
5. Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
The tested injected doses of 99mTc-DARPinG3 3000 μg (SPECT)	99mTc-DARPinG3	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.

Primary Outcome Measures

Name	Time	Method
SPECT-based tumor-to-background ratio (conventional units)	4 hours	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
SPECT/CT-based 99mTc-DARPinG3 uptake value in primary tumor (standardized uptake value (SUV))	4 hours	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

Secondary Outcome Measures

Name	Time	Method
Tumor-to-background ratio 99mTc-DARPinG3 SPECT versus immunohistochemical study	4 hours	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

Trial Locations

Locations (2)

Tomsk NRMC; 🇷🇺 Tomsk, Russian Federation

TomskNRMC; 🇷🇺 Tomsk, Russian Federation