68Ga-NY104 PET/CT and Conventional Imaging in Patients With Von Hippel-Lindau Disease: a Prospective, Single-center, Single-arm, Comparative Imaging Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- The number of (68Ga-NY104) PET positive patients
研究概览
简要总结
This is a prospective, single-center, single-arm, diagnostic phase 2 study in patients with von Hippel-Lindau disease. VHL disease is a rare syndrome characterized by VHL gene mutation and HIF activation. Although genetic testing is available, the manifestations of the syndrome are protean; therefore, imaging plays a crucial role in the identification of abnormalities and subsequent follow-up of lesions. For now, conventional imaging serves as the main radiologic modality in the characterization of VHL disease. In this study, we aim to evaluate the sensitivity of 68Ga-NY104 PET/CT in patients with VHL disease. 68Ga-NY104 is a novel small molecule PET tracer targeting carbonic anhydrase IX, which is a down-streaming target of HIF and overexpressed in HIF activation. 68Ga-NY104 PET/CT is likely to function as a sensitive imaging tool to identify VHL-related tumors and to impact patient management if additional lesions are identified.
The hypotheses of this study are that
- 68Ga-NY104 PET/CT can be used as an effective imaging modality in VHL syndrome with high sensitivity
- 68Ga-NY104 PET/CT may detect lesions that are missed on conventional imaging and can result in management impact.
A total of 19 patients will be recruited at Peking Union Medical College Hospital. As an exploratory end-point, a 68Ga-NODAGA-LM3 PET/CT sub-study will be performed in patients with evidence of neuroendocrine tumors.
详细描述
Hypothesis
The hypotheses of this study are that
- 68Ga-NY104 PET/CT can be used as an effective imaging modality in VHL syndrome with high sensitivity
- 68Ga-NY104 PET/CT may detect lesions that are missed on conventional imaging and can result in management impact.
Objectives
Primary objective 1. To determine the sensitivity of 68Ga-NY104 PET/CT using conventional imaging as reference.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of VHL disease, according to 2022 CSCO guideline, if any one of the following criteria is met: germline VHL alteration, family history of VHL syndrome as well as presence of at least one VHL related tumor (including hemangioblastoma, clear cell renal cell tumor, pheochromocytoma, paraganglioma, pancreatic neuroendocrine tumor, etc.), two or more hemangioblastoma, hemangioblastoma and pheochromocytoma, hemangioblastoma and clear cell renal cell tumor.
- •Written informed consent provided for participation in the trial
- •In the opinion of investigator, willing and able to comply with required study procedures.
排除标准
- •Patients on VEGF TKI treatment < 1 week before 68Ga-NY104 PET/CT. TKI is known to affect girentuximab binding in patients with ccRCC and is expected to have the same effect on 68Ga-NY
- •If patients were on VEGF TKI treatment, such as sunitinib, sorafenib, cabozantinib, pazopanib, or lenvatinib, a washout of one week before 68Ga-NY104 PET/CT is required.
- •Patients on HIF antagonist treatment < 3 months before 68Ga-NY104 PET/CT. CA9, which encodes carbonic anhydrase IX (CAIX), is one of the genes most strongly upregulated by HIF-
- •HIF antagonist, such as Belzutifan, might affect the expression of CAIX and thus the binding of 68Ga-NY104 to tumor. Withdraw of at least 3 months is required for HIF antagonist.
- •Patients with known allergic reaction to CT or MR contrast medium.
- •Patients with renal dysfunction
- •Pregnancy or breastfeeding.
- •Severe claustrophobia.
- •If the patient will undergo an exploratory 68Ga-NODGA-LM3 PET/CT and is on cold somatostatin analogue (such as Octreotide and Lanreotide), the 68Ga-NODGA-LM3 should be injected at least 24 hours after cold somatostatin analogue injection. Patients violating this criteria will not be able to attend the exploratory 68Ga-NODGA-LM3 PET/CT study but will still be considered eligible for the main study.
研究组 & 干预措施
Diagnostic imaging arm
68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis 68Ga-NODAGA-LM3 PET/CT (exploratory)
干预措施: 68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis) 68Ga-NODAGA-LM3 PET/CT (exploratory) (Diagnostic Test)
结局指标
主要结局
The number of (68Ga-NY104) PET positive patients
时间窗: From study completion to 1 month after completion
Any patient with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related patient
Binary reading of lesions identified on 68Ga-NY104 PET/CT
时间窗: From study completion to 1 month after completion
Define lesion as PET positive or PET negative lsion
The number of (68Ga-NY104) PET positive lesions
时间窗: From study completion to 1 month after completion
Count the number of lesions (if more than 10, record it as \>10)
The number of (68Ga-NY104) PET positive regions
时间窗: From study completion to 1 month after completion
Any region with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related region
Scoring of lesions identified on conventional imaging as very unlikely / unlikely / indeterminate / likely / very likely (score 1-5)
时间窗: From study completion to 1 month after completion
The likelihood of VHL-related neoplasm will be rated combining all imaging features available, including enhancement pattern, typical location, and solitary or multicentric or bilateral distribution.
The number of conventional imaging positive lesions
时间窗: From study completion to 1 month after completion
Count the number of lesions (if more than 10, record it as \>10)
The number of conventional imaging positive regions
时间窗: From study completion to 1 month after completion
Any region with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related region
The number of conventional imaging positive patients
时间窗: From study completion to 1 month after completion
Any patient with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related patient
次要结局
- The intent of initial management plan (Plan 1) based on conventional imaging(From study completion to 1 month after completion)
- The intent of post-PET management plan (Plan 2) based on all information available, including the results of conventional imaging, 68Ga-NY104 PET/CT, and additional confirmatory studies.(From study completion to 1 month after completion)
- The specified management plan of initial management plan (Plan 1) based on conventional imaging(From study completion to 1 month after completion)
- The specified management plan of post-PET management plan (Plan 2) based on all information available, including the results of conventional imaging, 68Ga-NY104 PET/CT, and additional confirmatory studies.(From study completion to 1 month after completion)