A First-in-Human, Phase I PET Imaging Study of 11C-YJH08, a Selective Glucocorticoid Receptor-Targeting Agent, in Patients With Advanced Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Median Percent Change From Baseline at the Time of Progression in Standardized Uptake Value (SUV)Max-ave (Cohort B and C Only)
研究概览
简要总结
This phase I trial studies if positron emission tomography (PET) imaging using 11C-YJH08 can be useful for detecting certain cell receptor expression in tumor cells in patients with cancer that has spread to other parts of the body (metastatic). 11C-YJH08 is a small-molecule radiotracer that binds to receptors on cells (glucocorticoid receptor) so that they show up better on the PET scan. Systemic therapy (including enzalutamide) can cause more glucocorticoid receptors to be produced in tumor cells, which can make the tumor cells resist hormone therapies. If researchers can find a better way to detect whether glucocorticoid receptors are increasing during therapy, it may lead to more successful therapies using glucocorticoid receptor antagonists.
详细描述
PRIMARY OBJECTIVES:
I. To determine the feasibility of metastatic lesion detection in enzalutamide/apalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC) using 11C-YJH08 PET. (Cohort A).
II. To determine the mean percent change from baseline at the time of progression on enzalutamide or apalutamide in standardized uptake value (SUV)max-ave on paired 11C-YJH08 PET on a per-patient and per-lesion basis. (Cohorts B & C).
SECONDARY OBJECTIVES:
I. To determine the safety and determine average organ uptake of 11C-YJH08. II. To descriptively report the patterns of intra-tumoral uptake of 11C-YJH08 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Disease characteristics by cohort, as defined by:
- •COHORT A: Histologically confirmed metastatic solid tumor malignancy.
- •COHORT B: Metastatic castration-resistant prostate cancer with progression on systemic therapies by Prostate Specific Antigen Working Group 3 (PSAWG3).
- •COHORT C: Metastatic advanced solid tumor malignancy other than prostate adenocarcinoma with at least one metastasis on conventional imaging.
- •The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Age 18 years or older at the time of study entry.
- •Adequate organ function, as defined by:
- •Serum creatinine =< 1.5 x upper limit of normal (ULN) OR estimated creatinine clearance > 50 ml/min
- •Total bilirubin =< 1.5 x ULN
- •Hemoglobin >= 8.0 g/dL
- •Platelet count >= 50,000/microliter
- •Absolute neutrophil count >= 1000/microliter
排除标准
- •Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Concurrent treatment with any dose of systemic glucocorticoids within 7 days prior to cycle 1 day 1 (C1D1).
- •History of adrenal insufficiency requiring use of systemic glucocorticoid replacement.
- •History of Cushing's disease or Cushing's syndrome.
- •Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures.
- •Contra-indication to MRI (e.g. pacemaker placement, severe claustrophobia) (applicable only for patients scheduled for PET/MRI).
研究组 & 干预措施
Cohort A: Any Solid Tumor (Dosimetry Cohort)
Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.
干预措施: Computed Tomography (Procedure)
Cohort A: Any Solid Tumor (Dosimetry Cohort)
Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort A: Any Solid Tumor (Dosimetry Cohort)
Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.
干预措施: Positron Emission Tomography (Procedure)
Cohort A: Any Solid Tumor (Dosimetry Cohort)
Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.
干预措施: 11C-YJH08 (Drug)
Cohort A: Any Solid Tumor (Dosimetry Cohort)
Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.
干预措施: Optional Tumor Biopsy (Procedure)
Cohort B: Metastatic CRPC
Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Computed Tomography (Procedure)
Cohort B: Metastatic CRPC
Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort B: Metastatic CRPC
Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Positron Emission Tomography (Procedure)
Cohort B: Metastatic CRPC
Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: 11C-YJH08 (Drug)
Cohort B: Metastatic CRPC
Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Optional Tumor Biopsy (Procedure)
Cohort C: Solid Tumor Malignancy
Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Computed Tomography (Procedure)
Cohort C: Solid Tumor Malignancy
Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort C: Solid Tumor Malignancy
Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Positron Emission Tomography (Procedure)
Cohort C: Solid Tumor Malignancy
Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: 11C-YJH08 (Drug)
Cohort C: Solid Tumor Malignancy
Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.
干预措施: Optional Tumor Biopsy (Procedure)
结局指标
主要结局
Median Percent Change From Baseline at the Time of Progression in Standardized Uptake Value (SUV)Max-ave (Cohort B and C Only)
时间窗: Up to 24 months
The median percent change from baseline, and range of SUVmax-ave (in each study cohort) will be descriptively reported using mediastinal blood pool and normal organ as background uptake values.
Sensitivity of 11C-YJH08 PET in Metastatic Lesion Detection (Cohort A Only)
时间窗: Up to day 1 follow-up
Using as a cut-off to define a positive lesion on PET as a lesion with SUV at least 1.5 times higher than mediastinal blood pool, the sensitivity (probability that a test will indicate recurrent disease among those with recurrent disease (True Positive / (True Positive + False Negative)) will be descriptively reported on a lesion-per-lesion basis, using as reference standard staging scans including computed tomography or magnetic resonance imaging of the chest/abdomen/pelvis.
Median Percent Change From Baseline in Standardized Uptake Value (SUV)Max (Cohort B and C Only)
时间窗: Up to 24 months
The median percent change from baseline, and range of SUVmax (across all metastatic lesions per patient) will be descriptively reported using mediastinal blood pool and normal organ as background uptake values.
次要结局
- Median Intra-tumoral Uptake(Up to 24 months)
- Association Between Baseline Uptake on 11C-YJH08 PET With Prostate Specific Antigen (PSA50) Response (Cohort B Only )(Up to 24 months)
- Number of Participants With Reported Treatment-emergent Adverse Events(Up to day 1 after injection)
- Association Between Baseline Uptake on 11C-YJH08 PET and Clinical Benefit Rate (Cohort B & C Only)(Up to 24 months)
- Association Between Baseline Uptake on 11C-YJH08 PET and Objective Response Rate (Cohort B & C Only)(Up to 24 months)
- Median Progression-free Survival by Cohort (Cohort B & C Only)(Up to 24 months)
研究者
Rahul Aggarwal
Principal Investigator
University of California, San Francisco