HER2 Expression Detection and Radionuclide Therapy in Breast Cancer Using 99mTc/188Re Labeled Single Domain Antibody

NCT ID: NCT04674722

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-24

Study Completion Date

2024-10-30

Brief Summary

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To evaluate the safety, dosimetry and efficacy of 99mTc/188Re labeled anti-HER2-single domain antibody (Product Code Name: 99mTc-NM-02 and 188Re-NM-02) SPECT/CT imaging of HER2 expression and radionuclide therapy in Breast Cancer. The SPECT/CT results will compare with the existing gold standard " HER2 expression detection" by biopsy tissue immunohistochemistry (IHC) and/or Fluorescence in Situ Hybridization (FISH) method, and 18F-FDG PET/CT imaging. It also to establish a new theranostic method for non-invasive HER2 expression detection and radionuclide therapy in breast cancer using 99mTc/188Re labeled anti-HER2 single domain antibody.

Detailed Description

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Anti-HER2 single domain antibody will be labeled with 99mTc and 188Re to prepare 99mTc-NM-02 and 188Re-NM-02, respectively. 99mTc-NM-02 is used as a diagnostic agent for SPECT/CT imaging of HER2 expression, and 188Re-NM-02 is used as a therapeutic drug for radionuclide therapy of HER2-postive Breast Cancer.

Conditions

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Breast Cancer Radiotoxicity

Keywords

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HER2 single domain antibody SPECT/CT imaging Radionuclide therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Injection of 99mTc-NM-02

All breast cancer patients recruited to the study will be administered 3-12 MBq/kg of 99mTc-NM-02 (99mTc labeled anti-HER2 sdAb) in a single dose injection.

Group Type EXPERIMENTAL

Injection of 99mTc-NM-02

Intervention Type DRUG

A Patient will be injected with microdose (\<100ug) of 99mTc-NM-02 radiotracer

Injection of 188Re-NM-02

Ten breast cancer patients recruited to the study will be administered 66 MBq/kg of 188Re-NM-02 (188Re labeled anti-HER2 sdAb) in a single dose injection.

Group Type EXPERIMENTAL

Injection of 188Re-NM-02

Intervention Type DRUG

A Patient will be injected with microdose (\<100ug) of 188Re-NM-02 radionuclide therapy

Interventions

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Injection of 99mTc-NM-02

A Patient will be injected with microdose (\<100ug) of 99mTc-NM-02 radiotracer

Intervention Type DRUG

Injection of 188Re-NM-02

A Patient will be injected with microdose (\<100ug) of 188Re-NM-02 radionuclide therapy

Intervention Type DRUG

Other Intervention Names

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anti-HER2 SPECT/CT radiotracer anti-HER2 radionuclide therapy

Eligibility Criteria

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Inclusion Criteria

1. Adult female, age 18 years or older
2. Prior diagnosis of breast cancer
3. Willing to participate in this study and given written informed consent
4. AST, ALT, BUN, Cr not more than double the normal values
5. Subjects of childbearing potential must be willing to undergo a pregnancy test prior to enrolment

Patients will only be included in the 188Re-NM-02 study if they meet the following supplementary criterial: HER2 postive, progression or recurrence after standard treatment, including surgery, chemotherapy, radiotherapy and targeted therapy.

Exclusion Criteria

1. Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period)
2. Breastfeeding (subjects in lactation)
3. No biopsy tissue sample can be provided for HER2 expression detection
4. Subjects with pacemakers
5. Hepatitis B virus infection (including carriers) at screening, ie hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (anti-HCV) positive, or acquired immunodeficiency disease (HIV) infected, or serum syphilis positive person
6. Abnormal liver function during baseline screening period : AST or ALT\> 2 times the upper limit of normal value (ULN), if the marginal increase of a single index is judged as having no clinical significance by the investigator, it can be retested during the screening period. Once, if ≤ 2 times ULN after retesting, consider enrolling).
7. Impaired renal function during screening: serum creatinine or urea nitrogen \> 1.5 times ULN.
8. Within 4 months prior to the baseline screening period , myocardial infarction or other cardiac events requiring hospitalization (unstable angina, etc.), cerebrovascular accident, transient ischemic attack, acute congestive Heart failure or severe arrhythmia (ventricular arrhythmia, atrioventricular block above II)
9. Subjects with pulmonary embolism or deep vein thrombosis
10. Various infections that the investigators consider unsuitable for study, including but not limited to patients with various infections requiring further treatment, such as urinary tract infections, respiratory infections, and diabetic foot infections.
11. Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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NanoMab Technology (UK) Limited

INDUSTRY

Sponsor Role collaborator

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Zhao Jin Hua, MD

Director of Department of Nuclear Medicine, Principal Investigator, Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jinhua Zhao, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Nuclear Medicine, Shanghai General Hospital

Locations

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Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

References

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Harbeck N, Gnant M. Breast cancer. Lancet. 2017 Mar 18;389(10074):1134-1150. doi: 10.1016/S0140-6736(16)31891-8. Epub 2016 Nov 17.

Reference Type BACKGROUND
PMID: 27865536 (View on PubMed)

Keyaerts M, Xavier C, Heemskerk J, Devoogdt N, Everaert H, Ackaert C, Vanhoeij M, Duhoux FP, Gevaert T, Simon P, Schallier D, Fontaine C, Vaneycken I, Vanhove C, De Greve J, Lamote J, Caveliers V, Lahoutte T. Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma. J Nucl Med. 2016 Jan;57(1):27-33. doi: 10.2967/jnumed.115.162024. Epub 2015 Oct 8.

Reference Type BACKGROUND
PMID: 26449837 (View on PubMed)

Baum RP, Prasad V, Muller D, Schuchardt C, Orlova A, Wennborg A, Tolmachev V, Feldwisch J. Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. J Nucl Med. 2010 Jun;51(6):892-7. doi: 10.2967/jnumed.109.073239. Epub 2010 May 19.

Reference Type BACKGROUND
PMID: 20484419 (View on PubMed)

Zhao L, Xing Y, Liu C, Ma S, Huang W, Cheng Z, Zhao J. Detection of HER2 expression using 99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial. Breast Cancer Res. 2024 Mar 8;26(1):40. doi: 10.1186/s13058-024-01803-y.

Reference Type DERIVED
PMID: 38459598 (View on PubMed)

Other Identifiers

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2020[84]

Identifier Type: -

Identifier Source: org_study_id