Clinical trial NCT05810246: 68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
Official title: 68Ga-NY104 PET/CT and Conventional Imaging in Patients With Von Hippel-Lindau Disease: a Prospective, Single-center, Single-arm, Comparative Imaging Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Von Hippel-Lindau Disease
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Secondary objectives

1. To determine the incremental management impact of 68Ga-NY104 PET/CT
2. To assess the interobserver agreement of 68Ga-NY104 PET/CT by comparing the two blinded independent readings

Exploratory objective

1. To compare the per-patient, per-region, and per-lesion sensitivity of 68Ga-NY104 PET/CT to 68Ga-NODAGA-LM3 PET/CT in an exploratory endpoint

Endpoints

Primary endpoint 1. Per-patient, per-region, and per-lesion positive rate of 68Ga-NY104 using conventional imaging as ground truth.

Secondary endpoints

1. Incremental impact of 68Ga-NY104 PET/CT on choice of management, defined as a decision to alter the original plan of treatment (based on conventional imaging) after considering the result of 68Ga-NY104 PET/CT (Impact is categorized as high, medium, low or no incremental impact.)
2. Observer agreement in interpretation of 68Ga-NY104 PET/CT between the two independent nuclear medicine readers.

Exploratory endpoints

1. Per-patient, per-region, and per-lesion positive rate of 68Ga-NODAGA-LM3 using conventional imaging as ground truth.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Age ≥ 18 y
3. Written informed consent provided for participation in the trial
4. In the opinion of investigator, willing and able to comply with required study procedures.

Exclusion Criteria:

1. 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-NY104. 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.
2. 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-1. 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.
3. Patients with known allergic reaction to CT or MR contrast medium.
4. Patients with renal dysfunction
5. Pregnancy or breastfeeding.
6. Severe claustrophobia.
7. 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.

Primary outcomes:
measure: Binary reading of lesions identified on 68Ga-NY104 PET/CT
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NY104) PET positive lesions
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NY104) PET positive regions
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NY104) PET positive patients
timeFrame: From study completion to 1 month after completion
measure: Scoring of lesions identified on conventional imaging as very unlikely / unlikely / indeterminate / likely / very likely (score 1-5)
timeFrame: From study completion to 1 month after completion
measure: The number of conventional imaging positive lesions
timeFrame: From study completion to 1 month after completion
measure: The number of conventional imaging positive regions
timeFrame: From study completion to 1 month after completion
measure: The number of conventional imaging positive patients
timeFrame: From study completion to 1 month after completion
Secondary outcomes:
measure: The intent of initial management plan (Plan 1) based on conventional imaging
timeFrame: From study completion to 1 month after completion
measure: 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.
timeFrame: From study completion to 1 month after completion
measure: The specified management plan of initial management plan (Plan 1) based on conventional imaging
timeFrame: From study completion to 1 month after completion
measure: 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.
timeFrame: From study completion to 1 month after completion
Other outcomes:
measure: Binary reading of lesions identified on 68Ga-NODAGA-LM3 PET/CT as PET positive lesions or PET negative lesions
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NODAGA-LM3) PET positive lesions
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NODAGA-LM3) PET positive regions
timeFrame: From study completion to 1 month after completion
measure: The number of (68Ga-NODAGA-LM3) PET positive patients
timeFrame: From study completion to 1 month after completion
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Uion Medical College Hospital
name: Li Huo, MD
role: PRINCIPAL_INVESTIGATOR
References: