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

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.

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Female
• Intervention / Treatment: Drug: 99mTc-ADAPT6; Drug: 99mTc-DARPinG3

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Tomsk, Russian Federation, 634005
    • Tomsk NRMC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subject is > 18 years of age;
2. Diagnosis of primary breast cancer with possible lymph node metastases before system (chemo+targeted therapy);
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. Sequential injection of 99mTc-ADAPT6 and 99mTc-DARPinG3 in the interval of 3-4 days in each HER2-positive breast cancer patient;

5. 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
6. 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:

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

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 21, 2023

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; 99mTc-ADAPT6; HER2 expression; 99mTc-DARPinG3
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 99mTc-ADAPT6 vs 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