A First-in-Human, Pilot PET Imaging Study of 89Zr-DFO-YS5, an immunoPET Agent for Detecting CD46 Positive Malignancy in Men With Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Optimal time point for imaging using 89Zr-DFO-YS5 PET post-injection (Cohort A)
研究概览
简要总结
CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials. The hypothesis of the study is that CD46 expression, measured via our novel imaging biomarker, is a characteristic feature of mCRPC, and particularly common in the most lethal forms of the disease including adenocarcinoma and Small-cell neuroendocrine carcinoma (SCNC). These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development of novel therapeutic and theranostic agents, to help develop treatments that improve outcomes for men with the most lethal forms of prostate cancer.
详细描述
This single center imaging study involves one microdose of the imaging agent, followed by whole body PET imaging. Imaging data will be acquired in up to four PET studies to determine tumor and normal tissue uptake and dosimetry.
PRIMARY OBJECTIVES:
- To determine the optimal time point for imaging (based on analyzing the 4 scans of all participants using 89Zr-DFO-YS5 PET post-injection). (Cohort A)
- To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B).
- To determine the sensitivity of metastatic lesion detection in mCRPC using 89Zr-DFO-YS5 PET as compared with conventional imaging (Cohorts C)
SECONDARY OBJECTIVES:
- To determine the safety of 89Zr-DFO-YS5.
- To determine average organ uptake of 89Zr-DFO-YS5 (Cohort C).
- To descriptively report the patterns of intra-tumoral uptake of 89Zr-DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal (Cohorts C).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically or cytologically confirmed metastatic, castration resistant prostate cancer (mCRPC).
- •Age >=18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >60%).
- •Demonstrates adequate organ function as defined below:
- •Total bilirubin <1.5 X upper limit of normal (ULN).
- •Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase (SGOT)) <= 3 X institutional upper limit of normal (ULN).
- •Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) <= 3 X institutional ULN.
- •Serum creatinine <=1,5 X institutional ULN or calculated creatinine clearance (Glomerular filtration rate (GFR)) >= 60 mL/min, calculated using the Cockcroft-Gault equation.
- •Ability to understand a written informed consent document, and the willingness to sign it.
- •Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
排除标准
- •Patients who because of age, general medical, or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
研究组 & 干预措施
Cohort A: 89Zr-DFO-YS5
Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total. The optimized scan time will be used for imaging in cohorts B and C. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: 89Zr-DFO-YS5 (Drug)
Cohort A: 89Zr-DFO-YS5
Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total. The optimized scan time will be used for imaging in cohorts B and C. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Computerized tomography (CT) (Procedure)
Cohort A: 89Zr-DFO-YS5
Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total. The optimized scan time will be used for imaging in cohorts B and C. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) (Procedure)
Cohort B: 89Zr-DFO-YS5, YS5 antibody
Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C & D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: 89Zr-DFO-YS5 (Drug)
Cohort B: 89Zr-DFO-YS5, YS5 antibody
Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C & D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: YS5 antibody (Biological)
Cohort B: 89Zr-DFO-YS5, YS5 antibody
Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C & D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Computerized tomography (CT) (Procedure)
Cohort B: 89Zr-DFO-YS5, YS5 antibody
Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C & D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) (Procedure)
Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody
Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: 89Zr-DFO-YS5 (Drug)
Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody
Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: YS5 antibody (Biological)
Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody
Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Computerized tomography (CT) (Procedure)
Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody
Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
干预措施: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) (Procedure)
结局指标
主要结局
Optimal time point for imaging using 89Zr-DFO-YS5 PET post-injection (Cohort A)
时间窗: Up to 7 days
For Cohort A, the optimal time point will be selected based on optimal maximun Standardized uptake value (SUVmax) of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.
Optimal antibody dose for imaging using 89Zr-DFO-YS5 PET (Cohort B)
时间窗: Up to 7 days
For Cohort B, the optimal dose of antibody will be selected based on the optimal SUVmax of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.
Proportion of participants with metastatic lesions accurately detected in mCRPC using 89Zr-DFO-YS5 PET (sensitivity) (Cohort C)
时间窗: Up to 24 months
Sensitivity is the probability that a test will indicate disease among those with the actual disease: True Positive / (True Positive + False Negative). Lesions will be graded on a semi-quantitative scale ranging from 1-5 as is common for 89Zr-antibody human imaging studies (1 = no uptake, 2 = probably no uptake, 3 = equivocal, 4 = probably positive, 5 = definitely positive). Using as a cut-off to 4 or 5 on the semi-quantitative scale, the sensitivity of 89Zr-DFO-YS5 PET will be descriptively reported on a lesion-per-lesion basis, using as reference standard staging scans including CT or MRI of the chest/abdomen/pelvis and whole body bone scan. The sensitivity estimate will be based on lesion level without considering the location of the lesions or the possible intra-correlation of the lesions from the same patient.
Median SUVmax (Cohort C)
时间窗: Up to 24 months
The median and range of SUVmax across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values will be reported with range of SUVmax.
Average SUVmax (SUVmax-ave) (Cohort C)
时间窗: Up to 24 months
The average SUVmax-ave across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values for all cohorts will be reported with 95% confidence intervals
次要结局
- Proportion of participants with treatment-related Adverse Events(Up to 3 weeks after last dose administration, approximately 35 days)
- Average organ uptake of 89Zr-DFO-YS5 (Cohort C)(Up to 24 months)
- Intra-tumoral uptake of 89Zr-DFO-YS5 by tumor type (Cohort C)(Up to 24 months)
- Intra-tumoral uptake of 89Zr-DFO-YS5 by Site of Disease (Cohort C)(Up to 24 months)
- Inter-tumoral heterogeneity (Cohort C)(Up to 24 months)
- Inter-participant heterogeneity (Cohort C)(Up to 24 months)
- Tumor-to-background signal (Cohort C)(Up to 24 months)
研究者
Robert Flavell, MD, PhD
Principal Investigator
University of California, San Francisco