Breast CancerEarly Phase 1NCT04674722
HER2 Expression Detection and Radionuclide Therapy in Breast Cancer Using 99mTc/188Re Labeled Single Domain Antibody
A Early Phase 1 study testing Injection of 99mTc-NM-02 and Injection of 188Re-NM-02 in people with Breast Cancer and Radiotoxicity, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Radiotoxicity
- What is being tested?
- Injection of 99mTc-NM-02 and Injection of 188Re-NM-02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteChina
- Study dates
- 24 Aug 2020to 30 Oct 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer, Radiotoxicity
- Being tested
- Injection of 99mTc-NM-02, Injection of 188Re-NM-02
- Keywords
- HER2, single domain antibody, SPECT/CT imaging, Radionuclide therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection of 99mTc-NM-02Drug
Also called anti-HER2 SPECT/CT radiotracer
A Patient will be injected with microdose (<100ug) of 99mTc-NM-02 radiotracer
Injection of 188Re-NM-02Drug
Also called anti-HER2 radionuclide therapy
A Patient will be injected with microdose (<100ug) of 188Re-NM-02 radionuclide therapy
| Study group | Role | What they receive |
|---|---|---|
| Injection of 99mTc-NM-02 | Experimental | 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. Receives: Drug: Injection of 99mTc-NM-02 |
| Injection of 188Re-NM-02 | Experimental | 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. Receives: Drug: Injection of 188Re-NM-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
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.
Measured: 2 years
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.
Measured: 2 years
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
Measured: 2 years
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.
Measured: 2 years
Secondary outcomes (1)
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start24 Aug 2020
- Primary completion8 May 2024
- Study completion30 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- NanoMab Technology (UK) Limited
- Responsible party
- Principal investigator, Zhao Jin Hua, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- Investigators
- Jinhua Zhao, PhD, Principal investigator, Department of Nuclear Medicine, Shanghai General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04674722
- Sponsor's protocol ID
- 2020[84]
- Status last verified
- Dec 2024
- First submitted
- 14 Dec 2020
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 27865536Keyaerts 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.
PubMed 26449837Baum 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.
PubMed 20484419Zhao 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.
PubMed 38459598
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04674722
- Acronym / sponsor ID
- 2020[84]
- Conditions
- Breast Cancer, Radiotoxicity
- Keywords
- HER2, single domain antibody, SPECT/CT imaging, Radionuclide therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- NanoMab Technology (UK) Limited
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- 8 May 2024 (actual)
- Study completion
- 30 Oct 2024 (actual)
- First posted
- 19 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Injection of 99mTc-NM-02 | Experimental | Drug: Injection of 99mTc-NM-02All 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. |
| Injection of 188Re-NM-02 | Experimental | Drug: Injection of 188Re-NM-02Ten 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injection of 99mTc-NM-02Also: anti-HER2 SPECT/CT radiotracerA Patient will be injected with microdose (<100ug) of 99mTc-NM-02 radiotracer | Drug | Injection of 99mTc-NM-02 |
| Injection of 188Re-NM-02Also: anti-HER2 radionuclide therapyA Patient will be injected with microdose (<100ug) of 188Re-NM-02 radionuclide therapy | Drug | Injection of 188Re-NM-02 |
Primary outcome
Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan
Time frame: 1 year
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
Time frame: 2 years
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
Time frame: 2 years
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
Time frame: 2 years
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
Time frame: 2 years
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.
1 secondary outcome
Therapeutic evaluation of HER2 overexpressed Breast Cancer using 188Re-NM-02
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Background: PubMed 27865536Harbeck 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.
- Background: PubMed 26449837Keyaerts 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.
- Background: PubMed 20484419Baum 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.
- Derived from this study: PubMed 38459598Zhao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jinhua Zhao, PhD principal investigator
Department of Nuclear Medicine, Shanghai General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Injection of 99mTc-NM-02 and Injection of 188Re-NM-02 in people with Breast Cancer and Radiotoxicity, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan (time frame: 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04674722, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.