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

NCT04277338 | Completed Phase 1

• 1 other identifier: Molecular imaging of HER2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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:

1. 1.To assess distribution of 99mTc-HE3-G3 in normal tissues and in tumours over time;
2. 2.To evaluate dosimetry of 99mTc-HE3-G3;
3. 3.To obtain initial information concerning safety and tolerability of 99mTc-HE3-G3 after single intravenous injection:

Conditions

Primary Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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

  6 hours

• 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

  6 hours

• 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

  6 hours

• 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)

  6 hours

Secondary Outcomes (4)

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

  24 hours

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

  24 hours

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

  24 hours

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

  24 hours

Study Arms (3)

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

EXPERIMENTAL

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 Subjects withdrawn from the study for any reason will be replaced.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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Interventions

SPECT DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

TomskNRMC

Tomsk, Russia

Location

Related Publications (1)

• 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.

  PMID: 34385343 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Vladimir I Chernov

  Tomsk NRMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 20, 2020
• Study Start: February 10, 2020
• Primary Completion: February 10, 2021
• Study Completion: October 4, 2021
• Last Updated: October 6, 2021

Record last verified: 2021-10

Locations

RU (1)