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

Primary Purpose

Breast Cancer, Radiotoxicity

Status

Recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Injection of 99mTc-NM-02

Injection of 188Re-NM-02

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring HER2, single domain antibody, SPECT/CT imaging, Radionuclide therapy

Eligibility Criteria

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

Inclusion Criteria:

Adult female, age 18 years or older
Prior diagnosis of breast cancer
Willing to participate in this study and given written informed consent
AST, ALT, BUN, Cr not more than double the normal values
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:

Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period)
Breastfeeding (subjects in lactation)
No biopsy tissue sample can be provided for HER2 expression detection
Subjects with pacemakers
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
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).
Impaired renal function during screening: serum creatinine or urea nitrogen > 1.5 times ULN.
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)
Subjects with pulmonary embolism or deep vein thrombosis
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.
Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)

Sites / Locations

Shanghai General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Injection of 99mTc-NM-02

Injection of 188Re-NM-02

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan

Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99m-Tc-NM-02 in breast malignant lesions. A 4-point system will be used to interpret the scans for abnormalities. It is categorised as such: score 0, no abnormal increased uptake; score 1, low increased uptake; score 2, moderate increased uptake; score 3, high increased uptake. The lesion will be considered positive for malignancy if the score is 2 or higher.

Semiquantitative Assessment of Breast and other Metastatic Lesions in 99mTc-NM-02 SPECT/CT Scan

Each subject will be administered 3-12 MBq/kg of 99mTc-NM-02 and the semiquantitative analysis of the region of interest (ROI) will be performed in breast and other metastatic lesions. Higher level of HER2 expression (Tumor proportion score, TPS), higher ROI in tumor. 18F-FDG PET/CT, HER2 IHC and/or FISH used as comparators.

Safety of 99mTc-NM-02 through Adverse Event Monitoring

Subjects will be observed for safety after administration of 99mTc-NM-02, and will do follow up at 7 days p.i. Subjects will do blood test to observe for abnormalities in clinical parameters and compare to baseline results.

Changes of 99mTc-NM-02 uptake

The changes of tumor volume and maximum standard uptake value (SUVmax) will be recorded in primary and metastatic lesions

Safety of 188Re-NM-02 through Adverse Event Monitoring

Subjects will be observed for safety after administration of 188Re-NM-02, and will do follow up at 28 days p.i. Subjects will be contacted by investigator by phone and asked several questions related to subject's health after 188Re-NM-02 injection and concomitant drugs.

Secondary Outcome Measures

Therapeutic evaluation of HER2 overexpressed Breast Cancer using 188Re-NM-02

Ten patients will be administered 66 MBq/kg of 188Re-NM-02, and the changes of tumor volume and maximum standard uptake value (SUVmax) will be recorded in breast and other metastatic lesions to analyze treatment effect.

Full Information

NCT ID

NCT04674722

First Posted

December 14, 2020

Last Updated

April 13, 2023

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

NanoMab Technology (UK) Limited

1. Study Identification

Unique Protocol Identification Number

NCT04674722

Brief Title

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

Official Title

Technetium-99m/Rhenium-188 Labeled Anti-HER2 Single Domain Antibody (99mTc/188Re-NM-02) for HER2 Expression Detection and Radionuclide Therapy in Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 24, 2020 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

NanoMab Technology (UK) Limited

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

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

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.

6. Conditions and Keywords

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

Breast Cancer, Radiotoxicity

Keywords

HER2, single domain antibody, SPECT/CT imaging, Radionuclide therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Injection of 99mTc-NM-02

Arm Type

Experimental

Arm Description

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.

Arm Title

Injection of 188Re-NM-02

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Injection of 99mTc-NM-02

Other Intervention Name(s)

anti-HER2 SPECT/CT radiotracer

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Injection of 188Re-NM-02

Other Intervention Name(s)

anti-HER2 radionuclide therapy

Intervention Description

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

Primary Outcome Measure Information:

Title

Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan

Description

Time Frame

1 year

Title

Semiquantitative Assessment of Breast and other Metastatic Lesions in 99mTc-NM-02 SPECT/CT Scan

Description

Time Frame

2 years

Title

Safety of 99mTc-NM-02 through Adverse Event Monitoring

Description

Time Frame

2 years

Title

Changes of 99mTc-NM-02 uptake

Description

The changes of tumor volume and maximum standard uptake value (SUVmax) will be recorded in primary and metastatic lesions

Time Frame

2 years

Title

Safety of 188Re-NM-02 through Adverse Event Monitoring

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Therapeutic evaluation of HER2 overexpressed Breast Cancer using 188Re-NM-02

Description

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult female, age 18 years or older Prior diagnosis of breast cancer Willing to participate in this study and given written informed consent AST, ALT, BUN, Cr not more than double the normal values 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: Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period) Breastfeeding (subjects in lactation) No biopsy tissue sample can be provided for HER2 expression detection Subjects with pacemakers 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 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). Impaired renal function during screening: serum creatinine or urea nitrogen > 1.5 times ULN. 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) Subjects with pulmonary embolism or deep vein thrombosis 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. Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jinhua Zhao, PhD

Phone

0086-21-37798352

zhaojinhua1963@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Lingzhou Zhao, PhD

Phone

0086-21-37798354

zlz-330@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jinhua Zhao, PhD

Organizational Affiliation

Department of Nuclear Medicine, Shanghai General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shanghai General Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jinhua Zhao, PhD

Phone

0086-21-37798352

zhaojinhua1963@126.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

27865536

Citation

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.

Results Reference

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PubMed Identifier

26449837

Citation

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.

Results Reference

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PubMed Identifier

20484419

Citation

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.

Results Reference

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

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