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

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

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.

Study Overview

• Status: Completed
• Conditions: Female; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: 99mTc-DARPinG3

Detailed Description

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

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Russian Federation
  • Tomsk, Russian Federation
    • TomskNRMC
  • Tomsk, Russian Federation
    • Tomsk NRMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Breast cancer female patients.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The tested injected doses of 99mTc-DARPinG3 3000 μg (SPECT); 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; Diagnostic test (99mTc-DARPinG3-based SPECT) is used for the assessment of the effect of anticancer therapy.; Other Names: Diagnostic injection of 99mTc-DARPinG3.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
• Collaborators: Uppsala University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2 expression; 99mTc-DARPinG3; chemotherapy and targeted therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 99mTc-DARPinG3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No