99mTc-ADAPT6 SPECT-based Non-invasive Quantification of HER2-expression in Breast Cancer With Metastatic Lymph Nodes (99mTc-ADAPT6)

SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Primary Tumour and Metastatic Axillary Lymph Nodes Using Technetium-99m-labelled ADAPT6 Molecule-based 99mTc-ADAPT6.

An open-label, single center study with 99mTc-ADAPT6 SPECT and biopsies of primary tumour and metastatic lymph nodes in breast cancer patients, where the primary endpoint of the study is to find out the correlation between the HER2 expression measured by 99mTc-ADAPT6 SPECT and standard histopathology from relevant tumor and lymph node biopsies.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Female
• Intervention / Treatment: Drug: ADAPT6-SPECT

Detailed Description

Overall goal of the project: To determine HER2 expression level in primary breast cancer and axillary lymph node metastases before neoadjuvant targeted (trastuzumab or trastuzumab+pertuzumab) therapy.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Olga Bragina, MD, PhD; Phone Number: +79627761423; Email: rungis@mail.ru
• Study Contact Backup: Name: Vladimir Chernov, MD, PhD; Phone Number: +73822426284; Email: chernov@tnimc.ru

Study Locations

• Russian Federation
  • Tomsk, Russian Federation
    • Tomsk NRMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 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 lymph node metastases
3. Availability of results from HER2 status previously determined on material from the primary tumor and metastatic LN, either a. HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or b. HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative

4. 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
5. 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. Any system therapy (chemo-/targeted therapy)
2. Second, non-breast malignancy
3. Active current autoimmune disease or history of autoimmune disease
4. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2-positive 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: ADAPT6-SPECT; Diagnostic SPECT for HER2 expression in primary tumour and metastatic lymph nodes; Other Names: Diagnostic ADAPT6-SPECT injection
Experimental: HER2-negative patients; Maximum 15 evaluable subjects with HER2-negative 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: ADAPT6-SPECT; Diagnostic SPECT for HER2 expression in primary tumour and metastatic lymph nodes; Other Names: Diagnostic ADAPT6-SPECT injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPECT/CT-based 99mTc-ADAPT6 uptake value in tumor lesions (SUV)	SPECT/CT-based 99mTc-ADAPT6 uptake value in tumor lesions measured as 99mTc-ADAPT6 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 hours after injection and measured in SUV	2 hours
SPECT/CT-based 99mTc-ADAPT6 uptake value in metastatic lymph nodes (SUV)	SPECT/CT-based 99mTc-ADAPT6 uptake value in metastatic lymph nodes SUV measured as 99mTc-ADAPT6 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2 hours after injection and measured in SUV	2 hours
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 (SUV) will be divided by the value of 99mTc-ADAPT6 uptake coinciding with the regions without pathological findings (SUV)	2 hours
LN-to-background LN ratio (SPECT)	The SPECT-based LN-to-background LN ratio will be calculated as follows: the value of 99mTc-ADAPT6 uptake coinciding with LN lesions (SUV) will be divided by the value of 99mTc-ADAPT6 uptake coinciding with the regions without pathological findings (SUV)	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Matching test rate (percentage)	Comparison of the 99mTc-ADAPT6 accumulation in the primary tumor and metastatic lymph nodes with the results of morphological and immunohistochemical studies.	2 hours

Collaborators and Investigators

• Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
• Collaborators: Uppsala University
• Investigators: Study Director: Vladimir I Chernov, MD, PhD, Caencer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Study record dates

Study Major Dates

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

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 (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; 99mTc-ADAPT6; metastatic lymph nodes; HER2 expression
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 99mTc-ADAPT6 in breast cancer

Drug and device information, study documents

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