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

Sponsor

Tomsk National Research Medical Center of the Russian Academy of Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT04277338

Collaborator

Institute of Bioorganic Chemistry, Russian Academy of Sciences (Other), Uppsala University (Other)

Enrollment

Location

Arms

19.8

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Breast Cancer	Drug: SPECT	Phase 1

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:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Diagnostic

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)

Actual Study Start Date :

Feb 10, 2020

Actual Primary Completion Date :

Feb 10, 2021

Actual Study Completion Date :

Oct 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: The tested injected doses of 99mTc-HE3-G3 1000 μg 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.	Drug: SPECT One single injection of 99mTc-HE3-G3, followed by gamma camera imaging directly postinjection and after 2, 4, 6 and 24 hours.
Experimental: The tested injected doses of 99mTc-HE3-G3 2000 μg 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.	Drug: SPECT One single injection of 99mTc-HE3-G3, followed by gamma camera imaging directly postinjection and after 2, 4, 6 and 24 hours.
Experimental: The tested injected doses of 99mTc-HE3-G3 3000 μg 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.	Drug: SPECT One single injection of 99mTc-HE3-G3, followed by gamma camera imaging directly postinjection and after 2, 4, 6 and 24 hours.

Arm

Intervention/Treatment

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

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.

Drug: SPECT

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

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

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.

Drug: SPECT

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

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

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.

Drug: SPECT

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

Outcome Measures

Primary Outcome Measures

Gamma camera-based whole-body 99mTc-HE3-G3 uptake value (%) [6 hours]
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) [6 hours]
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) [6 hours]
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) [6 hours]
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) [24 hours]
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) [24 hours]
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) [24 hours]
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) [24 hours]
The safety attributable to 99mTc-HE3-G3 injections will be evaluated based on the rate of administration of concomitant medication (%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts 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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TomskNRMC	Tomsk		Russian Federation

Sponsors and Collaborators

Tomsk National Research Medical Center of the Russian Academy of Sciences
Institute of Bioorganic Chemistry, Russian Academy of Sciences
Uppsala University

Investigators

Principal Investigator: Vladimir I Chernov, Tomsk NRMC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Tomsk National Research Medical Center of the Russian Academy of Sciences

ClinicalTrials.gov Identifier:

NCT04277338

Other Study ID Numbers:

Molecular imaging of HER2

First Posted:

Feb 20, 2020

Last Update Posted:

Oct 6, 2021

Last Verified:

Oct 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Tomsk National Research Medical Center of the Russian Academy of Sciences

99mTc-HE3-G3

Breast Cancer

HER2 expression

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Oct 6, 2021