Imaging of Solid Tumors Using FAP-2286
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Thomas Hope
- 入组人数
- 191
- 试验地点
- 2
- 主要终点
- Proportion of radiation-absorbed doses of radiolabeled FAP-2286 (Cohorts 1a/1b only)
研究概览
简要总结
This is a multi-arm prospective trial that evaluates the ability of a novel imaging radiolabeled agents to detect metastatic cancer in participants with solid tumors using a gallium 68 (68Ga-) or copper 64 (64Cu-) FAP-2286 tracer. FAP-2286 is a peptidomimetic molecule that that binds to Fibroblast Activation Protein (FAP). FAP is a transmembrane protein expressed on cancer-associated fibroblasts, and has been shown to be present on a number of solid tumors.
详细描述
Initially the investigator(s) will focus on imaging breast, pancreas, sarcoma, prostate cancer, bladder cancer, colon cancer, and head and neck cancer.
STUDY AIMS
- Determine the dosimetry for gallium-68 labelled (68Ga-) and 64Cu- FAP-2286.
- Evaluate the uptake and retention of radiotracer in a variety of solid tumors with FAP-2286.
- Evaluate the ability of FAP-2286 to detect metastatic disease.
PRIMARY OBJECTIVES
- All cohorts: Safety of 68Ga- and 64Cu-FAP-2286.
- Cohort 1a: determine the organ dosimetry of 68Ga-FAP-2286.
- Cohort 1b: determine the organ dosimetry of 64Cu-FAP-2286.
- Cohort 2: To assess the feasibility of detecting tumor uptake using FAP-2286.
- Cohort 3: To determine the feasibility of detecting metastatic disease using FAP-2286.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age >= 18 years.
- •Histopathologically confirmed solid tumors in one of the following cohorts:
- •a. Cohort 1 (n=11): measurable disease is not required for this cohort.
- •i. Agnostic to tumor type.
- •b. Cohort 2 (n=95): Metastatic disease present on conventional imaging defined as having RECIST 1.1 measurable disease or multiple bone metastases. Note: Presence of absence of metastatic disease for eligibility determination will be assessed by reviewing medical records. Screening imaging will not be conducted for this study.
- •i. Pathologically confirmed breast cancer, pancreatic adenocarcinoma, sarcoma, castrate-resistant prostate cancer, bladder cancer, colon cancer, or other cancer type.
- •c. Cohort 3 (n=85): No evidence of metastatic disease as defined as the absence of RECIST 1.1 measurable disease or bone metastases. Note: Presence of absence of metastatic disease for eligibility determination will be assessed by reviewing medical records. Screening imaging will not be conducted for this study.
- •i. Participants can be imaged at initial staging with what is judged by the treating physician to be high risk disease and where the presence of metastatic disease would greatly impact treatment planning and prognosis. Participants may also be imaged after therapy (surgery, chemotherapy or radiation therapy) if in the determination of the treating physician or investigator there is a high risk of disease recurrence that would also impact treatment plan and/or prognosis.
- •ii. Pathologically confirmed head and neck cancer, bladder cancer, or other cancer type.
- •Ability to understand a written informed consent document, and the willingness to sign it.
排除标准
- •Unlikely to comply with protocol procedures, restrictions and requirements and judged by the Investigator to be unsuitable for participation.
- •Known pregnancy.
研究组 & 干预措施
CLOSED - 64Cu-Dosimetry population (Cohort 1b)
PET imaging will begin 60±15 minutes, 240±30 minutes after injection, and a second PET imaging will be performed 24±2 hours after initial injection of 64Cu-FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Positron Emission Tomography (PET) imaging (Procedure)
CLOSED - 64Cu-Dosimetry population (Cohort 1b)
PET imaging will begin 60±15 minutes, 240±30 minutes after injection, and a second PET imaging will be performed 24±2 hours after initial injection of 64Cu-FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Copper-64 labeled (64Cu-) FAP-2286 (Drug)
CLOSED - 68Ga-Dosimetry population (Cohort 1a)
PET imaging will begin 30 +/-10 minutes, 60 +/-15 minutes and 120 +/-20 minutes after injection of 68Ga-FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Gallium-68 labelled (68Ga-) FAP-2286 (Drug)
CLOSED - 68Ga-Dosimetry population (Cohort 1a)
PET imaging will begin 30 +/-10 minutes, 60 +/-15 minutes and 120 +/-20 minutes after injection of 68Ga-FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Positron Emission Tomography (PET) imaging (Procedure)
Participants with metastatic disease (Cohort 2)
Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Gallium-68 labelled (68Ga-) FAP-2286 (Drug)
Participants with metastatic disease (Cohort 2)
Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Positron Emission Tomography (PET) imaging (Procedure)
Participants with metastatic disease (Cohort 2)
Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.
干预措施: Copper-64 labeled (64Cu-) FAP-2286 (Drug)
Participants without metastatic disease (Cohort 3)
Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.
干预措施: Gallium-68 labelled (68Ga-) FAP-2286 (Drug)
Participants without metastatic disease (Cohort 3)
Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.
干预措施: Positron Emission Tomography (PET) imaging (Procedure)
Participants without metastatic disease (Cohort 3)
Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.
干预措施: Copper-64 labeled (64Cu-) FAP-2286 (Drug)
结局指标
主要结局
Proportion of radiation-absorbed doses of radiolabeled FAP-2286 (Cohorts 1a/1b only)
时间窗: Up to 3 days
Volumes of interest of 68Ga- and 64Cu- will be drawn around regions identified on the scans, including the liver, spleen, kidneys, urinary bladder, the central sacrum (for hematopoietic marrow) and whole body. Data will be fitted using the Simulation, Analysis, and Modeling Software II (SAAM II) software. Time integrals of activity will be entered into the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) software, using the reference adult model. The results from all patients enrolled will be combined to allow the calculation of mean, standard deviation (SD), and range of radiation-absorbed doses to individual organs
Standardized Uptake Values (SUVs) (Cohort 2 only)
时间窗: Up to 3 days
The maximum Standardized Uptake Value (SUVmax) will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity.
Tumor-to-background (TBR) Ratio (Cohort 2 only)
时间窗: Up to 3 days
TBR ratios will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity. The median and range of the measured TBRs will be reported across all RECIST measurable lesions as a table broken down by location (organ metastases, nodal metastases and bone metastases).
Proportion of positive lesions on FAP-2286 PET (Cohort 3 only)
时间窗: Up to 3 days
Conventional imaging or CT portion of PET/CT scan will be reviewed in conjunction with the FAP-2286 PET images. Lesions will be characterized as positive on FAP-2286 PET if uptake is greater than 1.5 times higher than mediastinal blood pool and uptake cannot be attributed to physiologic or inflammatory reasons. Conventional imaging or CT portion of PET/CT scan will be interpreted as positive by each lesion if the short axis dimension of lymph nodes is greater than 1 centimeter (cm), and organ metastases measure greater than 1 cm in long axis. The gold standard will be the combination of conventional imaging and FAP-2286 PET in combination with clinical follow-up and histopathology (if available). The number of lesions detected by each modality will be compared and sensitivity will be computed. Since this is a proof-of-concept study, it is not powered for the test of agreement. Nevertheless, the agreement will be tested using McNemar's test.
Count of participants with treatment-emergent adverse events
时间窗: Until end of day on the day of the injection (1 day total)
The frequency and severity of treatment emergent adverse events following FAP-2286 injection will be descriptively reported as classified and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Proportion of radiation-absorbed doses of radiolabeled FAP-2286 (Cohorts 1a/1b only)
时间窗: Up to 3 days
Volumes of interest of 68Ga- and 64Cu- will be drawn around regions identified on the scans, including the liver, spleen, kidneys, urinary bladder, the central sacrum (for hematopoietic marrow) and whole body. Data will be fitted using the Simulation, Analysis, and Modeling Software II (SAAM II) software. Time integrals of activity will be entered into the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) software, using the reference adult model. The results from all patients enrolled will be combined to allow the calculation of mean, standard deviation (SD), and range of radiation-absorbed doses to individual organs
Standardized Uptake Values (SUVs) (Cohort 2 only)
时间窗: Up to 3 days
The maximum Standardized Uptake Value (SUVmax) will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity.
Tumor-to-background (TBR) Ratio (Cohort 2 only)
时间窗: Up to 3 days
TBR ratios will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity. The median and range of the measured TBRs will be reported across all RECIST measurable lesions as a table broken down by location (organ metastases, nodal metastases and bone metastases).
Proportion of positive lesions on FAP-2286 PET (Cohort 3 only)
时间窗: Up to 3 days
Conventional imaging or CT portion of PET/CT scan will be reviewed in conjunction with the FAP-2286 PET images. Lesions will be characterized as positive on FAP-2286 PET if uptake is greater than 1.5 times higher than mediastinal blood pool and uptake cannot be attributed to physiologic or inflammatory reasons. Conventional imaging or CT portion of PET/CT scan will be interpreted as positive by each lesion if the short axis dimension of lymph nodes is greater than 1 centimeter (cm), and organ metastases measure greater than 1 cm in long axis. The gold standard will be the combination of conventional imaging and FAP-2286 PET in combination with clinical follow-up and histopathology (if available). The number of lesions detected by each modality will be compared and sensitivity will be computed. Since this is a proof-of-concept study, it is not powered for the test of agreement. Nevertheless, the agreement will be tested using McNemar's test.
次要结局
未报告次要终点
研究者
Thomas Hope
Principal Investigator
University of California, San Francisco