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Molecular Imaging of HER2 Expression in Breast Cancer Using 99mTc-HE3-G3 (HE3-G3)

Primary Purpose

Primary Breast Cancer

Status

Completed

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

SPECT

About this trial

This is an interventional diagnostic trial for Primary Breast Cancer focused on measuring 99mTc-HE3-G3, Breast Cancer, HER2 expression

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Subject is > 18 years of age
Diagnosis of primary breast cancer with possible lymph node metastases
Availability of results from HER2 status previously determined on material from the primary tumor, either
1. HER2-positive, defined as a immunohistochemical test score of 3+ or FISH positive or
2. HER2-negative, defined as a immunohistochemical test score of 0 or 1+; or else if 2+ then FISH negative
Volumetrically quantifiable tumour lesions on CT or MRI, with at least one lesion > 1.0 cm in greatest diameter outside of the liver and kidneys
Hematological, liver and renal function test results within the following limits:
- White blood cell count: > 2.0 x 10^9/L
- Haemoglobin: > 80 g/L
- Platelets: > 50.0 x 10^9/L
- Bilirubin =< 2.0 times Upper Limit of Normal
- Serum creatinine: Within Normal Limits
A negative pregnancy test (serum beta-human chorionic gonadotropin, beta-HCG) at screening 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)
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

Sites / Locations

TomskNRMC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

The tested injected doses of 99mTc-HE3-G3 1000 μg

The tested injected doses of 99mTc-HE3-G3 2000 μg

The tested injected doses of 99mTc-HE3-G3 3000 μg

Arm Description

At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. The tested injected dose 1000 μg. Subjects withdrawn from the study for any reason will be replaced.

At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. The tested injected dose 2000 μg. Subjects withdrawn from the study for any reason will be replaced.

At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. The tested injected dose 3000 μg. Subjects withdrawn from the study for any reason will be replaced.

Outcomes

Primary Outcome Measures

Gamma camera-based whole-body 99mTc-HE3-G3 uptake value (%)

Whole-body 99mTc-HE3-G3 uptake coinciding with normal organs and tissues will be assessed using gamma camera and calculated as percentage (%) of the injected dose of the radiopharmaceutical

SPECT-based 99mTc-HE3-G3 uptake value in tumor lesions (counts)

99mTc-HE3-G3 uptake coinciding with tumor lesions will be assessed using single-photon emission computed tomography and measured in counts

SPECT-based 99mTc-HE3-G3background uptake value (counts)

Focal uptake of 99mTc-HE3-G3 in the regions without pathological findings will be assessed with SPECT and measured in counts

Tumor-to-background ratio (SPECT)

The SPECT-based tumor-to-background ratio will be calculated as follows: the value of 99mTc-HE3-G3 uptake coinciding with tumor lesions (counts) will be divided by the value of 99mTc-HE3-G3 uptake coinciding with the regions without pathological findings (counts)

Secondary Outcome Measures

Safety attributable to 99mTc-HE3-G3 injections (physical findings)

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the assessments of physical examination, vital signs, and ECG (% of cases with abnormal findings relative to baseline)

Safety attributable to 99mTc-HE3-G3 injections (laboratory tests)

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the blood and urine laboratory tests (% of cases with abnormal findings relative to baseline)

Safety attributable to 99mTc-HE3-G3 injections (incidence and severity of adverse events)

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the rate of adverse events (%)

Safety attributable to 99mTc-HE3-G3 injections (concomitant medication)

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the rate of administration of concomitant medication (%)

Full Information

NCT ID

NCT04277338

First Posted

February 10, 2020

Last Updated

October 4, 2021

Sponsor

Tomsk National Research Medical Center of the Russian Academy of Sciences

Collaborators

Institute of Bioorganic Chemistry, Russian Academy of Sciences, Uppsala University

1. Study Identification

Unique Protocol Identification Number

NCT04277338

Brief Title

Molecular Imaging of HER2 Expression in Breast Cancer Using 99mTc-HE3-G3

Acronym

HE3-G3

Official Title

SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Breast Cancer Using Technetium-99m-labelled Designed Ankyrin Repeat Proteins HE3-G3 (99mTc-HE3-G3)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

February 10, 2020 (Actual)

Primary Completion Date

February 10, 2021 (Actual)

Study Completion Date

October 4, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tomsk National Research Medical Center of the Russian Academy of Sciences

Collaborators

Institute of Bioorganic Chemistry, Russian Academy of Sciences, Uppsala University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The study should evaluate distribution of 99mTc-HE3-G3 in patients with primary HER2-positive and HER2-negative breast cancer. The primary objective are: To assess distribution of 99mTc-HE3-G3 in normal tissues and in tumours over time; To evaluate dosimetry of 99mTc-HE3-G3; To obtain initial information concerning safety and tolerability of 99mTc-HE3-G3 after single intravenous injection: The secondary objective are: 1.To compare the tumour imaging data with the concerning HER2 expression obtained by immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH) analysis of biopsy samples.

Detailed Description

Overall goal of the project: To determine HER2 expression level in primary breast cancer and possibly in axillary lymph node metastases before neoadjuvant trastuzumab therapy. Phase I. Distribution of 99mTc-HE3-G3 in patients with primary breast cancer. The study should evaluate distribution of 99mTc-HE3-G3 in patients with primary HER2-positive and HER2-negative breast cancer. The primary objective are: To assess distribution of 99mTc-HE3-G3 in normal tissues and in tumours over time; To evaluate dosimetry of 99mTc-HE3-G3; To obtain initial information concerning safety and tolerability of 99mTc-HE3-G3 after single intravenous injection: The secondary objective are: 1. To compare the tumour imaging data with the concerning HER2 expression obtained by immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH) analysis of biopsy samples: Methodology: Open-label, exploratory, single centre study. The subjects will receive a single injection of the labelled tracer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Breast Cancer

Keywords

99mTc-HE3-G3, Breast Cancer, HER2 expression

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

The tested injected doses of 99mTc-HE3-G3 1000 μg

Arm Type

Experimental

Arm Description

Arm Title

The tested injected doses of 99mTc-HE3-G3 2000 μg

Arm Type

Experimental

Arm Description

At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. The tested injected dose 2000 μg. Subjects withdrawn from the study for any reason will be replaced.

Arm Title

The tested injected doses of 99mTc-HE3-G3 3000 μg

Arm Type

Experimental

Arm Description

At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. The tested injected dose 3000 μg. Subjects withdrawn from the study for any reason will be replaced.

Intervention Type

Drug

Intervention Name(s)

SPECT

Intervention Description

One single injection of 99mTc-HE3-G3, followed by gamma camera imaging directly postinjection and after 2, 4, 6 and 24 hours.

Primary Outcome Measure Information:

Title

Gamma camera-based whole-body 99mTc-HE3-G3 uptake value (%)

Description

Whole-body 99mTc-HE3-G3 uptake coinciding with normal organs and tissues will be assessed using gamma camera and calculated as percentage (%) of the injected dose of the radiopharmaceutical

Time Frame

6 hours

Title

SPECT-based 99mTc-HE3-G3 uptake value in tumor lesions (counts)

Description

99mTc-HE3-G3 uptake coinciding with tumor lesions will be assessed using single-photon emission computed tomography and measured in counts

Time Frame

6 hours

Title

SPECT-based 99mTc-HE3-G3background uptake value (counts)

Description

Focal uptake of 99mTc-HE3-G3 in the regions without pathological findings will be assessed with SPECT and measured in counts

Time Frame

6 hours

Title

Tumor-to-background ratio (SPECT)

Description

Time Frame

6 hours

Secondary Outcome Measure Information:

Title

Safety attributable to 99mTc-HE3-G3 injections (physical findings)

Description

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the assessments of physical examination, vital signs, and ECG (% of cases with abnormal findings relative to baseline)

Time Frame

24 hours

Title

Safety attributable to 99mTc-HE3-G3 injections (laboratory tests)

Description

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the blood and urine laboratory tests (% of cases with abnormal findings relative to baseline)

Time Frame

24 hours

Title

Safety attributable to 99mTc-HE3-G3 injections (incidence and severity of adverse events)

Description

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the rate of adverse events (%)

Time Frame

24 hours

Title

Safety attributable to 99mTc-HE3-G3 injections (concomitant medication)

Description

The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the rate of administration of concomitant medication (%)

Time Frame

24 hours

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject is > 18 years of age Diagnosis of primary breast cancer with possible lymph node metastases Availability of results from HER2 status previously determined on material from the primary tumor, either HER2-positive, defined as a immunohistochemical test score of 3+ or FISH positive or HER2-negative, defined as a immunohistochemical test score of 0 or 1+; or else if 2+ then FISH negative Volumetrically quantifiable tumour lesions on CT or MRI, with at least one lesion > 1.0 cm in greatest diameter outside of the liver and kidneys Hematological, liver and renal function test results within the following limits: White blood cell count: > 2.0 x 10^9/L Haemoglobin: > 80 g/L Platelets: > 50.0 x 10^9/L Bilirubin =< 2.0 times Upper Limit of Normal Serum creatinine: Within Normal Limits A negative pregnancy test (serum beta-human chorionic gonadotropin, beta-HCG) at screening 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) 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vladimir I Chernov

Organizational Affiliation

Tomsk NRMC

Official's Role

Principal Investigator

Facility Information:

Facility Name

TomskNRMC

City

Tomsk

Country

Russian Federation

12. IPD Sharing Statement

Citations:

PubMed Identifier

34385343

Citation

Bragina O, Chernov V, Schulga A, Konovalova E, Garbukov E, Vorobyeva A, Orlova A, Tashireva L, Sorensen J, Zelchan R, Medvedeva A, Deyev S, Tolmachev V. Phase I Trial of 99mTc-(HE)3-G3, a DARPin-Based Probe for Imaging of HER2 Expression in Breast Cancer. J Nucl Med. 2022 Apr;63(4):528-535. doi: 10.2967/jnumed.121.262542. Epub 2021 Aug 12.

Results Reference

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Molecular Imaging of HER2 Expression in Breast Cancer Using 99mTc-HE3-G3

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