Technetium-99m/Rhenium-188 Labeled Anti-HER2 Single Domain Antibody (99mTc/188Re-NM-02) for HER2 Expression Detection and Radionuclide Therapy in Breast Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Safety of 188Re-NM-02 through Adverse Event Monitoring
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Injection of 99mTc-NM-02 (Drug)
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.
干预措施: Injection of 188Re-NM-02 (Drug)
结局指标
主要结局
Safety of 188Re-NM-02 through Adverse Event Monitoring
时间窗: 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.
Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 2 years
The changes of tumor volume and maximum standard uptake value (SUVmax) will be recorded in primary and metastatic lesions
次要结局
- Therapeutic evaluation of HER2 overexpressed Breast Cancer using 188Re-NM-02(3 years)
研究者
Zhao Jin Hua, MD
Director of Department of Nuclear Medicine, Principal Investigator, Professor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine